ВАКЦИНЫ ПРОТИВ МАЛЯРИИ

Изобретение относится к области биотехнологии и молекулярной биологии. Предложена вирусоподобная частица для вакцинации против малярии, которая содержит структурный полипептид вируса, полученный из вируса Чикунгунья (CHIKV) или вируса венесуэльского энцефалита лошадей (VEEV), и по меньшей мере один антиген малярии, где указанный структурный полипептид вируса содержит по меньшей мере один первый участок присоединения в белке оболочки и указанный по меньшей мере один антиген малярии содержит по меньшей мере один второй участок присоединения, указанный антиген малярии является антигеном, содержащим (NPNA), где n составляет от 4 до 30, и/или антиген содержит (EYLNKIQNSLSTEWSPCSVT), где y составляет от 1 до 6, и указанный структурный полипептид вируса и указанный антиген малярии связаны посредством указанного по меньшей мере одного первого и указанного по меньшей мере одного второго участков присоединения. Изобретение может быть использовано в медицине для борьбы с малярией. 6 н. и 6 з.п. ф-лы ...

ВАКЦИННАЯ КОМПОЗИЦИЯ, ОБЛАДАЮЩАЯ СВОЙСТВОМ ВЫЗЫВАТЬ ЦИТОЛИТИЧЕСКИЙ Т-КЛЕТОЧНЫЙ ОТВЕТ У МЛЕКОПИТАЮЩИХ, СПОСОБ ПОЛУЧЕНИЯ ЦИТОЛИТИЧЕСКОГО Т-КЛЕТОЧНОГО ОТВЕТА IN VIVO, СПОСОБ ПОЛУЧЕНИЯ ВАКЦИНЫ

Изобретение относится к медицине, а именно к вакцинной композиции, включающей антиген, 3-де-O-ацилированный монофосфориллипид-А и QS 21 в качестве адъюванта. Данная вакцинная композиция обладает свойством вызывать цитолитический Т-клеточный ответ у млекопитающих. Раскрыт способ получения данной вакцины путем смешивания антигена с 3Д-МФЛ в водной суспензии, а затем вводят QS 21 в водном растворе с хлоридом натрия при рН 6,5+0,5. Вакцинная композиция обладает свойством индуцировать более широкий спектр иммунных ответов, чем известные. 3 с. и 5 з.п.ф-лы, 2 табл.

СПОСОБЫ ВАКЦИНАЦИИ ПРОТИВ МАЛЯРИИ

Изобретение относится к биотехнологии и медицине. Способ по изобретению включает примирование антималярийного иммунного отклика с помощью вакцины, основанной на ДНК, и стимулирование этого отклика с помощью вакцины на белковой основе. Описана вакцина, включающая, в качестве отдельных компонентов, примирующий состав, включающий, по крайней мере, один полинуклеотид, кодирующий, по крайней мере, один первый малярийный антиген, и стимулирующий состав, состоящий из, по крайней мере, одного полипептида, дополнительно включающего, по крайней мере, один второй малярийный антиген. Раскрыт набор для иммунизации человека против вызывающего малярию патогена. Изобретение позволяет расширить получаемый иммунный отклик с помощью повторной иммунизации (стимулирования) вакциной на белковой основе. 4 н. и 40 з.п. ф-лы, 12 ил., 5 табл.

ВАКЦИННАЯ КОМПОЗИЦИЯ, ПРИМЕНЕНИЕ КОМПОЗИЦИИ, СПОСОБЫ ЛЕЧЕНИЯ, СПОСОБ ПРИГОТОВЛЕНИЯ КОМПОЗИЦИИ

Изобретение создает вакцинные композиции, включающие 3 де-о-ацилированный монофосфориллипид А и QS 21. Эти вакцинные композиции являются мощными индукторами ЦТЛ- и интерферон гамма-ответов.

MOLEKUELE MIT MINDESTENS EINER PEPTIDSEQUENZ EINER ODER MEHRERER EPITOPEN EINES P.FALCIPARUM-PRODUZIERTEN PROTEINS IN HEPATOZYTEN UND ZUSAMMENSETZUNGEN DAVON.

STRESS-PROTEINE EPITOPEN

Rekombinanter MVA Virus und seine Verwendung

MALARIA-VAKZINE

RHOPTRY ANTIGEN OF PLASMODIUM FALCIPARUM

Vaccine

The present invention relates to a fowlpox virus genome which has modifications in one or more wild-type FPV genes. The present invention also relates to a viral particle comprising such a genome and its use to deliver a nucleotide of interest (NOI) to a target cell. The present invention also relates to vaccination methods, particularly a method which comprises administering a priming composition (which comprises a first non-replicating viral vector) and a boosting composition (which comprises a second non-replicating viral vector) to a subject to treat and/or prevent a disease.

Screening method for novel vaccine candidates and compositions obtained thereby

NOVEL PROTEIN

Vaccine for falciparum malaria

INFECTIOUS PLASMODIUM SPOROZOITES GROWN IN VITRO

MALARIA VACCINE

Polynucleotides and polypeptides involved in gestational malaria, and biological applications

Vaccines against pregnancy-associated malaria

Univeral t-cell epitopes for anti-malarial vaccines

VACCINE AND METHOD OF PREPARATION

Adjuvant for transcutaneous immunization

Vaccine.

A polypeptide ...

Vaccine.

An ...

Universal T-cell epitopes for anti-malarial vaccines.

The present invention provides methods and compositions for eliciting protective immunity against malaria. In particular, the invention relates universal t-cell epitopes that elicit t-cell responses in individuals of differing genetic backgrounds. Immunogenic compositions and vaccines comprising malaria-specific universal t-cell epitopes are disclosed.

Vaccine composition against malaria.

A vaccine composition useful in the prvention of treatment of malaria comprises a plurality of malaria-derived angtigens in combination 1 with an adjuvant which is a preferential stimulator of th1 cell response.

Vaccine composition containing adjuvants.

The present invention provides vaccine compositions comprising 3de-o-acylated monophosphoryl lipid a and qs21. The vaccines compositions are potent inducers of ctl and yifn responses.

Induction of cytotoxic T- lymphocite responses.

Methods and compositions useful for inducing a cyctotoxic t-lymphocyte (ctl)in a human or domesticated or agriculturally important animal. The method includes the steps of providing the antigen to which the ctl response is desired and providing an antigen formulation which comprises, consists, or consists essentially of two or more of a stabilizing detergent, a micelle-forming agent, and an oil. This antigen formulation is preferably lacking in an immunostimulating peptide component, or has sufficiently low levels of such a component that the desired ctl response is not diminished. The formulation is provided as a stable oil-in-water emulsion.

Plasmodium circumsporozoite protein analogos lacking repeat sequences.

Recombinant immunogenic analogs of plasmodium circumsporozoite (CS) proteins useful as malaria subunit vaccines which lack one or more of the repeat epitopes of the native CS protein but have at least one nonrepeat flanking epitope from each of the amino terminal and carboxy terminal flanking regions of the native CS protein.

INFECTIOUS PLASMODIUM SPOROZOITES GROWN IN VITRO

Vaccine for falciparum malaria

MALARIA VACCINE

Method for the prevention of malaria

VACCINES AGAINST PREGNANCY-ASSOCIATED MALARIA

VACCINE

Univeral t-cell epitopes for anti-malarial vaccines

Vaccine composition against malaria

Polynucleotides and polypeptides involved in gestational malaria, and biological applications

Adjuvant for transcutaneous immunization.

A transcutaneous immunization system delivers antigen to immune cells without perforation of the skin, and induces an immune response in an animal or human. The system uses an adjuvant, preferably an adp-ribsylating exotoxin, to induce an antigen-specific immune response (e.G., humoral and/or cellular effectors)after trnascutaneous application of a formulation containing antigen and adjuvant to intact skin of the animal or human. The eficiency of immunization may be enhanced by adding hydrating agents (e.G. liposomes), penetration enhancers, or occlusive dressings to the transcutaneous delivery system. This system may allow activation of langerhans cells in the skin, migration of the langerhans cells to lymph nodes, and antigen presentation.

PLASMODIUM CIRCUMSPOROZOITE PROTEIN ANALOGS LACKING REPEAT SEQUENCES

Purified plasmodium and vaccine compositions

VACCINE

Vaccines containing a saponin and a sterol

Vaccines containing a saponin and a sterol.

The invention relates to a vaccine composition comprising an antigen, an immunoiogically active saponin fraction and a sterol.

Induction of cyctotoxi T-lymphocite responses

ROADMAP FOR CONTROLLING MALARIA

Vaccine and method of preparation.

A bacterial protein conjugatad to ...

VACCINES

Method to generate non virulent microorganisms from pathogenic ones through permanent genetic modification of their biological membrane for vaccine production.

Here we describe a methodology to generate non virulent microorganisms from pathogenic ones through permanent genetic modification of the physical state of their membrane (MPS). Thus, at the onset of infection, in these transformed organisms. as they infect a host (e.g. a target cell of a higher eukaryote, particularly mammals, and more specifically human cells, or injecting them, in a model of animal infection, the expression of heat shock (stress) genes and the accumulation of the coded proteins (stress proteins or HSPs) and that of other species-specific gene products, the regulation is altered as a consequence of the modification of MPS. Among others, we refer also to genes whose regulation is mediated by signaling transduction pathways. Therefore, as a result of this procedure, pathogens became non-virulent (attenuated, live microorganisms) that can be osed for vaccine production.

Vaccines for malaria

Vaccines for malaria

Malaria immunogen and vaccine

A chimeric, carboxy-terminal truncated hepatitis B virus nucleocapsid protein (IIBc) is disclosed that contains an immunogen for inducing the production of antibodies to malarial proteins. An immunogenic malarial epitope is expressed between residues 78 and 79 of the IIBc immunogenic loop sequence the chimer preferably contains a malaria-specific T cell epitope and is preferably engineered for both enhanced stability of self-assembled particles and enhanced yield of those chimeric particles. Methods of making and using the chimers are also disclosed.

Method for the prevention of malaria

Novel viral factor

Vaccines against pregnancy-associated malaria

Vaccines against pregnancy-associated malaria

Baculoviral vectors with a dual vertebrate and baculovirus promoter controlling an immunogenic fusion gene

Roadmap for controlling malaria

Vaccines

Vaccines

Polynucleotides and polypeptides involved in gestational malaria, and biological applications

Purified plasmodium and vaccine compositions.

Sequential polypeptides endowed with immunological activity

Immunogenic fraction activates with regard to the immunizing bilharzioses, its preparation, compositions containing it.

Vaccine composition against malaria

Vaccine.

Vaccine.

Method to generate non virulent microorganisms from pathogenic ones through permanent genetic modification of their biological membrane for vaccine production.

Vaccines for malaria.

Antigens of plasmodium falciparum.

Vaccine compositions containing liposomes.

Live genetically attenuated malaria vaccine.

Malaria associated antigen and preparing process thereof.

Expression of plasmodium falsoparum polypeptides from cloned CDNA.

Faction polypeptide inductive of protective antibodies against parasites of paludism and immunogenic compositions the container.

Method for the prevention of malaria.

Universal T-cell epitopes for anti-malarial vaccines.

Induction of cytotoxic t-lymphocyte responses

Malaria immunogen and vaccine.

Vaccines containing a saponin and a sterol

Induction of cytotoxic T-Lymphocyte Responses

Vaccines

Method for the prevention of malaria

Vaccines against pregnancy-associated malaria

Induction of cyctotoxi T-lymphocite responses

Vaccines containing a saponin and a sterol

PLASMODIUM CIRCUMSPOROZOITE PROTEIN ANALOGS LACKING REPEAT SEQUENCES

Vaccines for malaria

Vaccines for malaria

Vaccines against pregnancy-associated malaria

Purified plasmodium and vaccine compositions.

Method for the prevention of malaria

Vaccine composition against malaria

INFECTIOUS PLASMODIUM SPOROZOITES GROWN IN VITRO

Vaccine for falciparum malaria

VACCINE

VACCINE

MALARIA VACCINE

Vaccines against pregnancy-associated malaria

Roadmap for controlling malaria

VACCINES

Purified Plasmodium and Vaccine Compositions

Disclosed are substantially purified Plasmodium sporozoites and preparations of Plasmodium sporozoites substantially separated from attendant non-sporozoite material, where the preparations of Plasmodium sporozoites have increasing levels of purity. Vaccines and pharmaceutical compositions comprising purified Plasmodium sporozoites are likewise provided. Methods of purifying preparations of Plasmodium sporozoites are also provided.

Novel malaria vaccine

The present invention provides a vaccine for preventing and/or treating Plasmodium falciparum infections, which comprises a polypeptide set forth in SEQ ID NO: 1 or represented by formula (1), and an adjuvant. X 1 -A-B-X 2 -Y-X 3 -(Y)n-X 4 -(Y)n-X 5   (1) (In the formula, X 1 represents the 1st to 7th amino acid residues in a polypeptide set forth in SEQ ID NO: 1; X 2 represents the 73th to 177th amino acid residues; X 3 represents the 178th to 258th amino acid residues; X 4 represents the 259th to 289th amino acid residues; X 5 represents the 290th to 334th amino acid residues; A represents an 8-mer repeat sequence contained in a 47-kd region of SERA polypeptide of Plasmodium falciparum ; B represents a sequence of a serine-rich region contained in a 47-kd region of SERA polypeptide of Plasmodium falciparum ; Y represents any one selected from A-A, A-B, and B; and n is an integer of 0 or 1.)

Methods for the Prevention of Malaria

This application relates to preventing malaria by administering a vaccine. More particularly, this invention relates to a vaccine against malaria infection compromising the administration of attenuated sporozoites to a human or animal.

Pharmaceutical compositions comprising attenuated plasmodium sporozoites and glycolipid adjuvants

Disclosed herein are pharmaceutical compositions comprising Plasmodium sporozoite-stage parasites and compatible glycolipid adjuvants useful in vaccines for preventing or reducing the risk of malaria. In particular, human host range Plasmodium and analogues of α-galactosylceramide (α-GalCer), a ligand for natural killer T (NKT) cells, are combined in pharmaceutical compositions, which are useful as vaccines against malaria. Methods of use are also provided.

Plasmodium vivax Hybrid Circumsporozoite Protein and Vaccine

Described in this application is a synthetic P. vivax circumsporozoite protein useful as a diagnostic reagent, for antibody production, and as a vaccine protective against infection with any strain of P. vivax.

RECOMBINANT PLASMODIUM FALCIPARUM MEROZOITE SURFACE PROTEINS 4 AND 5 AND THEIR USE

Accordingly, the invention provides constructs in which the nucleic acids encoding MSP4 and MSP5, and the resulting polypeptides, have been modified. More particularly, this invention provides constructs encoding recombinant MSP4 and MSP5 polypeptides, which are expressed as soluble, secreted polypeptides in a baculovirus-insect cell expression system. It was surprisingly found that the recombinant polypeptides contain an EGF-like domain at the C-terminus that is properly folded in the polypeptide. 1. A purified nucleic acid molecule comprising the DNA sequence of SEQ ID NOS: 1 , 2 , 3 , 4 , 5 , 6 , 7 , 28 , 29 , or 8.2. A purified nucleic acid molecule encoding an amino acid sequence comprising the sequence of SEQ ID NOS: 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 30 , or 22.3. A purified nucleic acid molecule that hybridizes to either strand of a denatured , double-stranded DNA comprising the nucleic acid sequence of any one of or under conditions of moderate stringency in 50% formamide and 6×SSC , at 42° C. with washing conditions of 60° C. , 0.5×SSC , 0.1% SOS.4. The purified nucleic acid molecule as claimed in claim 3 , wherein said isolated nucleic acid molecule is derived by in vitro mutagenesis from SEQ ID NOS: 1-8.5. A purified nucleic acid molecule degenerate from SEQ ID NOS: 1 claim 3 , 2 claim 3 , 3 claim 3 , 4 claim 3 , 5 claim 3 , 6 claim 3 , 7 or 8 as a result of the genetic code.6. A purified nucleic acid molecule claim 3 , which encodes recombinant MSP4 or MSP5 polypeptide claim 3 , an allelic variant of recombinant MSP4 or MSP5 polypeptide DNA claim 3 , or a homolog of recombinant MSP4 or MSP5 polypeptide DNA.76. A recombinant vector that directs the expression of a nucleic acid molecule selected from the group consisting of the purified nucleic acid molecules of claim 3 , claim 3 , claim 3 , and .8. A recombinant vector that directs the expression of a nucleic acid molecule of .9. A recombinant vector that directs the ...

VACCINES AGAINST PREGNANCY-ASSOCIATED MALARIA

The present invention relates to specific regions of the N-terminal portion of the VAR2CSA protein and to the use of such specific regions in the prevention of pregnancy-associated malaria. The invention also provides immunogenic compositions and vaccines that are useful for preventing malaria in pregnant women. 1. An isolated polypeptide consisting of the NTS-DBL1x-Id1-DBL2x region of the VAR2CSA protein , or a biologically active fragment thereof , wherein the biologically active fragment comprises the Id1-DBL2x region of the VAR2CSA protein.2. The isolated polypeptide according to claim 1 , wherein the isolated polypeptide consists of the Id1-DBL2x region of the VAR2CSA protein.3. The isolated polypeptide according to claim 1 , wherein the Id1-DBL2x region of the VAR2CSA protein has the sequence set forth in SEQ ID NO: 2.4. The isolated polypeptide according to claim 1 , wherein the NTS-DBL1x-Id1-DBL2x region of the VAR2CSA protein has the sequence set forth in SEQ ID NO: 1.5. A fusion protein consisting of at least one polypeptide according to fused to at least one fusion partner for use in the treatment or prevention of pregnancy-associated malaria claim 1 , wherein the fusion partner is selected from the group consisting of maltose binding protein claim 1 , signal sequence of the maltose binding protein claim 1 , poly-histidine tag claim 1 , S-Tag claim 1 , glutathione-S-transferase claim 1 , thioredoxin claim 1 , β-galactosidase claim 1 , streptavidin claim 1 , dihydrofolate reductase claim 1 , pelB signal sequence claim 1 , ompA signal sequence claim 1 , signal sequence of alkaline phosphatase claim 1 , green fluorescent protein (GFP) claim 1 , toxins claim 1 , human growth hormone claim 1 , interleukin-2 (IL-2) claim 1 , granulocyte macrophage colony stimulating factor (GM-CSF) claim 1 , granulocyte colony stimulating factor (G-CSF) claim 1 , calcitonin claim 1 , interferon-beta claim 1 , interferon-alpha claim 1 , glucagon like peptide 1 (GLP-1) claim 1 , ...

MALARIA VACCINE

The present invention relates to a malaria vaccine comprising: 1. A malaria vaccine comprising:(a) a polypeptide consisting of an amino acid sequence of SEQ ID NO: 1, 2, or 3;{'i': 'falciparum', '(b) a polypeptide consisting of an amino acid sequence of SEQ ID NO: 1, 2, or 3, wherein one or more amino acids are deleted, substituted and/or added and having effect for preventing malaria; or'}{'i': 'falciparum', '(c) a polypeptide consisting of an amino acid sequence having 70% or more identity with an amino acid sequence of SEQ ID NO: 1, 2, or 3 and having effect for preventing malaria.'}2. A malaria vaccine according to claim 1 , wherein the polypeptide was synthesized by a wheat germ cell-free protein synthesis method.3. A malaria vaccine according to or claim 1 , further comprising an antibody involved in the sialic acid-dependent pathway.4. A malaria vaccine according to claim 3 , wherein the antibody involved in the sialic acid-dependent pathway is an anti-EBA-175 antibody.5falciparum. A method for preventing malaria claim 1 , comprising administrating a malaria vaccine according to to a subject in need such treatment. The present invention relates to a malaria vaccine.Malaria is widely spread in tropical and subtropical regions. Malaria is caused by infection with malaria parasites mediated by anopheles. Of four kinds of human malaria, and vivax malaria account for the majority of them. Both cause symptoms, such as fever and anemia. malaria causes death if accompanied by serious complications. After World War II, the number of deaths caused by malaria was reduced by measures against mediating mosquitoes using insecticides such as DDT and the appearance of a specific medicine, chloroquine. However, as chloroquine-resistant and insecticide-resistant mosquitoes subsequently emerged, the number of patients increased again. Currently, about 300 million people are affected by malaria, causing estimated deaths of more than 860,000 every year. Thus, malaria vaccines ...

PLANT-DERIVED CHOLERA AND MALARIA VACCINE

Described herein are methods for simultaneously immunizing a subject against Cholera and Malarial infection. Specifically exemplified herein are methods that involve administering compositions comprising a CTB-AMA1 or CTB-MSP1 derived from plants having plastids transformed to express such conjugates. 1. A method for increasing an immune response in a subject simultaneously against cholera infection and malarial infection , comprising administering to the subject an immunizing amount of a composition comprising CTB-AMA1 polypeptide , wherein said CTB-AMA1 polypeptide is derived from a plastid transformed to express said CTB-AMA1 polypeptide.2. (canceled)3. (canceled)4. A method for increasing an immune response in a subject simultaneously against cholera infection and malarial infection , comprising administering to the subject an immunizing amount of a composition comprising CTB-MSP1 polypeptide , wherein said CTB-MSP1 polypeptide is derived from a plastid transformed to express said CTB-MSP1 polypeptide.5. A composition derived from a plant , said composition effective in increasing an immune response in a subject against cholera and Malarial infection , said plant composition comprising a therapeutically effective amount of CTB-MSP1 polypeptide and rubisco.6. The composition of claim 5 , wherein said plant comprises a plastid transformed with a stable plastid transformation and expression vector which comprises an expression cassette comprising claim 5 , as operably linked components in the 5′ to the 3′ direction of translation claim 5 , a promoter operative in said plastid claim 5 , a selectable marker sequence claim 5 , a heterologous polynucleotide sequence coding for said CTB-MSP1 polypeptide claim 5 , transcription termination functional in said plastid claim 5 , and flanking each side of the expression cassette claim 5 , flanking DNA sequences which are homologous to a DNA sequence of the target plastid genome claim 5 , whereby stable integration of the ...

Lentiviral vector based immunological compounds against malaria

The invention relates to lentiviral vector particles pseudotyped with a determined heterologous viral envelope protein or viral envelope proteins originating from a RNA virus and which comprise in its genome at least one recombinant polynucleotide encoding at least one polypeptide(s) carrying epitope(s) of an antigen of a Plasmodium parasite capable of infecting a mammalian host. The lentiviral vector particles are used in order to elicit an immunological response against malaria parasites.

Treatment and Prevention of Malaria

There are provided antigens, vectors encoding the antigens, and antibodies and other binding compounds to the antigens and uses thereof in the prevention or treatment of malaria. In particular, compositions are provided comprising a Reticulocyte-binding protein Homologue 5 (PfRH5) antigen having at least 90% identity with SEQ ID NO: 1, or a fragment thereof; or which comprise a viral vector that expresses PfRH5 antigen having at least 90% identity with SEQ ID NO: 2, or a fragment thereof. 1. A vaccine composition comprising a Reticulocyte-binding protein Homologue 5 (PfRH5) antigen having at least 90% identity with amino acid residues 26 to 526 of SEQ ID NO: 1 or a fragment thereof that has a common antigenic cross-reactivity with said PfRH5 antigen.2. The composition of claim 1 , wherein the PfRH5 antigen or fragment thereof has an amino acid other than N at residue 38 and/or at amino acid residue 214 of SEQ ID NO: 1.3. The composition of claim 2 , wherein the PfRH5 antigen or fragment thereof has the amino acid Q at amino acid residue 38 and at amino acid residue 214 of SEQ ID NO: 1.4. The composition of claim 1 , wherein the composition further comprises one or more antigens from the group consisting of PfAMA1 claim 1 , PfEBA175 claim 1 , PfRH2a claim 1 , PfRH2b or PfRH4 claim 1 , or a fragment thereof.5. A viral vector or DNA plasmid that expresses PfRH5 antigen having at least 90% identity with SEQ ID NO: 2 or a fragment thereof that has a common antigenic cross-reactivity with said PfRH5 antigen.6. The viral vector or DNA plasmid of that expresses PfRH5 antigen having at least 90% identity with amino acid residues 34 to 534 of SEQ ID NO: 2 or a fragment thereof that has a common antigenic cross-reactivity with said PfRH5 antigen.7. The viral vector or DNA plasmid of claim 5 , wherein the viral vector or DNA plasmid expresses one or more antigens from the group consisting of PfAMA1 claim 5 , PfEBA175 claim 5 , PfRH2a claim 5 , PfRH2b or PfRH4 claim 5 , or a ...

Multicomponent vaccine for malaria providing long-lasting immune responses against plasmodia

Disclosed are immunogenic conjugates which elicit an immune response to Plasmodium proteins. In particular examples, the Plasmodium proteins include sexual stage surface proteins, circumsporozoite protein (CSP), or immunogenic portions of CSP. Also provided herein are immunogenic compositions including one or more of the disclosed immunogenic conjugates and a pharmaceutically acceptable carrier. Further provided is a method of eliciting an immune response to Plasmodium in a subject, comprising administering to the subject an immunogenic composition disclosed herein.

HETEROLOGOUS PRIME BOOST VACCINATION REGIMEN AGAINST MALARIA

Described are methods for inducing an immune response in a subject against an antigen from a malaria-causing parasite, preferably , the method comprising: (i) administering to a subject a priming composition comprising adjuvanted proteinaceous antigen-comprising circumsporozoite (CS) protein or an immunogenic part thereof from a malaria-causing parasite; (ii) administering to the subject a first boosting composition comprising a recombinant adenovirus vector that comprises nucleic acid encoding CS protein or immunogenic part thereof from a malaria-causing parasite; and (iii) administering to the subject a second boosting composition comprising a recombinant adenovirus vector that comprises nucleic acid encoding CS protein or an immunogenic part thereof from a malaria-causing parasite, wherein either the first boosting composition comprises a recombinant adenovirus vector of serotype 35 (Ad35) and the second boosting composition comprises a recombinant adenovirus of Ad26, or wherein the first boosting composition comprises a recombinant adenovirus vector of Ad26 and the second boosting composition comprises a recombinant adenovirus of Ad35. 1. A method for inducing an immune response in a subject against an antigen from a malaria-causing parasite , the method comprising:(i) administering to a subject a priming composition comprising adjuvanted proteinaceous antigen comprising circumsporozoite (CS) protein or an immunogenic part thereof from a malaria-causing parasite;(ii) administering to the subject a first boosting composition comprising a recombinant adenovirus vector that comprises nucleic acid encoding CS protein or an immunogenic part thereof from a malaria-causing parasite; and(iii) administering to the subject a second boosting composition comprising a recombinant adenovirus vector that comprises nucleic acid encoding CS protein or an immunogenic part thereof from a malaria-causing parasite,wherein either the first boosting composition comprises a recombinant ...

Purified Plasmodium and Vaccine Composition

Disclosed are substantially purified sporozoites and preparations of sporozoites substantially separated from attendant non-sporozoite material, where the preparations of sporozoites have increasing levels of purity. Vaccines and pharmaceutical compositions comprising purified sporozoites are likewise provided. Methods of purifying preparations of sporozoites are also provided. 147-. (canceled)48PlasmodiumPlasmodium. A method of conferring protective immunity in a human or other mammalian host against malaria caused by a -species parasite , said method comprising administering to said human or other mammalian host at least one dose of an aseptic , purified preparation of metabolically active , non-attenuated , infectious sporozoites concurrent with a regimen of administering an antimalarial agent , said purified preparation suitable for pharmaceutical use and comprising less than 85 nanograms of attendant material per 25 ,000 sporozoites; wherein protective immunity is conferred in said human or other mammalian host.49. The method of wherein said antimalarial agent is chloroquine.50PlasmodiumP. falciparum, P. vivax, P. malariae, P. ovaleP. knowlesi.. The method of wherein said host is human and the species of said aseptic claim 48 , purified claim 48 , non-attenuated claim 48 , infectious sporozoites is selected from the group consisting of claim 48 , and51PlasmodiumP. falciparum.. The method of wherein said species of sporozoite is52Plasmodium. The method of wherein said aseptic claim 48 , purified preparation of metabolically active claim 48 , non-attenuated claim 48 , infectious sporozoites is purified from mosquitoes.53Plasmodium. The method of wherein said aseptic claim 52 , purified preparation of metabolically active claim 52 , non-attenuated claim 52 , infectious sporozoites is purified from a pre-purification preparation of mosquito salivary gland material.54Plasmodium. The method of wherein said aseptic claim 48 , purified preparation of metabolically ...

Purified Plasmodium and Vaccine Composition

Disclosed are substantially purified sporozoites and preparations of sporozoites substantially separated from attendant non-sporozoite material, where the preparations of sporozoites have increasing levels of purity. Vaccines and pharmaceutical compositions comprising purified sporozoites are likewise provided. Methods of purifying preparations of sporozoites are also provided. 147-. (canceled)48PlasmodiumPlasmodium. A method of conferring protective immunity in a human or other mammalian host against malaria caused by a -species parasite , said method comprising administering to said human or other mammalian host at least one dose of an aseptic , purified preparation of metabolically active , attenuated sporozoites , said aseptic , purified preparation suitable for pharmaceutical use and comprising less than 85 nanograms of attendant material per 25 ,000 sporozoites , wherein protective immunity is conferred in said human or other mammalian host.49. The method of comprising administering at least 3 doses of said aseptic claim 48 , purified preparation.50. The method of comprising administering 5 or more doses of said aseptic claim 48 , purified preparation.51PlasmodiumPlasmodiumPlasmodium. The method of wherein said attenuation is established in said aseptic claim 48 , purified preparation of metabolically active claim 48 , attenuated sporozoites by exposure of a sporozoite to radiation claim 48 , mutagenic chemicals claim 48 , metabolically inhibiting chemicals claim 48 , adverse environmental conditions claim 48 , or by introducing a heritable genetic alteration claim 48 , deletion claim 48 , or mutation in the genome of said sporozoite.52Plasmodium. The method of wherein said attenuation is established by exposure of said sporozoite to radiation.53Plasmodium. The method of wherein said attenuation is established by exposure of said sporozoite to at least 120 Gy of radiation but no more than 200 Gy of radiation.54Plasmodium. The method of where said attenuation ...

PLASMODIUM FALCIPARUM CIRCUMSPOROZOITE VACCINE GENE OPTIMIZATION FOR SOLUBLE PROTEIN EXPRESSION

The present invention provides novel nucleotide sequence and other constructs used for expression of novel recombinant circumsporozoite proteins in bacterial cells such as Processes are provided for producing a soluble recombinant CSP from Methods to produce a human-grade, highly immunogenic anti-malaria vaccine based on CSP are shown. The novel recombinant circumsporozoite protein by itself or in combination with other malaria antigens or adjuvants can form the basis of an effective malaria vaccine. 1Plasmodium falciparum. A recombinant circumsporozoite protein (rCSP) , said rCSP characterized by:{'i': 'P. falciparum', 'an N-terminal region that lacks twenty to twenty-five N-terminus amino acid residues of native circumsporozoite protein;'}{'i': 'P. falciparum', 'a reduced number of NANP repeats compared to native circumsporozoite protein; and'}at least 85% homology to SEQ ID NO:2.2P. falciparumP. falciparum. The recombinant CSP of claim 1 , wherein the rCSP lacks Metto Cysof the N-terminal region of native circumsporozoite protein.3P. falciparum. The recombinant CSP of claim 1 , wherein the rCSP has 18 or 19 NANP repeats.4P. falciparum. The recombinant CSP of claim 3 , wherein the rCSP has 19 NANP repeats.5P. falciparum. The recombinant CSP of claim 1 , wherein the rCSP has a 0 to 3 NVDP repeats.6P. falciparum. The recombinant CSP of claim 5 , wherein the rCSP has 3 NVDP repeats.7P. falciparumP. falciparum. The recombinant CSP of claim 1 , wherein the rCSP has a C-terminal region that lacks ten to fourteen C-terminus amino acid residues of native circumsporozoite protein.8P. falciparum. The recombinant CSP of claim 7 , wherein the rCSP ends at Ser.9P. falciparum. The recombinant CSP of claim 1 , wherein the rCSP has at least 90% homology to SEQ ID NO:2.10P. falciparum. The recombinant CSP of claim 1 , wherein the rCSP has at least 95% homology to SEQ ID NO:2.11P. falciparum. The recombinant CSP of claim 1 , wherein the rCSP comprises SEQ ID NO:2.12P. falciparum. ...

Vaccine Composition

Disclosed are compositions and the use of the compositions for protection against pathogens comprising an isolated internal pathogenic protein, a TLR agonist and an aluminum salt. 1. A composition comprising an isolated internal pathogenic protein , a Toll-like receptor (TLR) agonist and an aluminum salt.2. The composition of claim 1 , wherein the isolated internal pathogenic protein is selected from the group consisting of influenza nucleoprotein (NP) claim 1 , matrix protein 1 (M1) claim 1 , matrix protein 2 (M2) claim 1 , non-structural-1 (NS1) claim 1 , non-structrual-2 (NS2) claim 1 , polymerase acidic (PA) claim 1 , polymerase basic 1 (PB 1) claim 1 , polymerase basic 1 F2 (PB2-F2) claim 1 , and polymerase basic 2 (PB2).3. The composition of claim 1 , wherein the isolated internal pathogenic protein is NP.4. The composition of claim 3 , wherein the NP is from influenza A.5. The composition of claim 1 , wherein the isolated internal pathogenic protein is from a pathogen selected from the group consisting of a virus claim 1 , parasite and bacteria.6. The composition of claim 1 , wherein the TLR agonist is selected from the group consisting of TLR1 claim 1 , TLR2 claim 1 , TLR3 claim 1 , TLR4 claim 1 , TLR5 claim 1 , TLR6 claim 1 , TLR7 claim 1 , TLR8 claim 1 , TLR9 claim 1 , TLR10 claim 1 , TLR11 claim 1 , TLR12 claim 1 , and TLR13.7. The composition of claim 6 , wherein the TLR agonist is selected from the group consisting of a lipopolysaccharide (LPS) derivative or mimetic claim 6 , monophosphoryl lipid A (MPL) or RC529.8. The composition of claim 7 , wherein the LPS derivative is MPL.9. The composition of claim 1 , wherein the aluminum salt is selected from the group consisting of alum claim 1 , potassium aluminum sulfate claim 1 , aluminum phosphate claim 1 , and aluminum hydroxide.10. The composition of claim 9 , wherein the aluminum salt is alum.11. The composition of claim 1 , wherein the composition may be administered to a subject orally claim 1 , ...

CONSENSUS ANTIGEN CONSTRUCTS AND VACCINES MADE THEREFROM, AND METHODS OF USING THE SAME TO TREAT MALARIA

Provided herein is consensus amino acid sequences of (P.f.) proteins and their encoding sequences, as well as expression constructs expressing the sequences. Also provided herein are methods for generating an immune response against using the expression constructs provided herein. 3. The vaccine of further comprising a nucleotide sequences that encodes IL-12 claim 1 , IL-15 claim 1 , IL-28B or RANTES.4. The vaccine of wherein said nucleotide sequences are incorporated into one or more plasmids.5P. falciparum. The vaccine of wherein said nucleotide sequences that encode each immunogen is incorporated a separate plasmid.6P. falciparum. The vaccine of wherein said nucleotide sequences that encode each immunogen are incorporated into two or more different plasmids.7. A method of immunizing a mammal against malaria comprising the step of administering the vaccine of to the tissue of the mammal.8. The method of comprising the steps ofa) administering the vaccine to the tissue of the mammal; andb) electroporating cells of the tissue with a pulse of energy at a constant current effective to permit entry of the nucleic acid molecules into the cells.9. The method of wherein vaccine is administered by intramuscular or intradermal injection.10. The method of wherein the current is preset for delivering to the tissue and pulse of energy is at a constant current that equals the preset current.11. The method of wherein the electroporating step further comprises:(a) measuring the impedence in the electroporated cells; and(b) adjusting the energy level of the pulse of energy relative to the measured impedance to maintain a constant current in the electroporated cells;wherein the measuring and adjusting steps occur within a lifetime of the pulse of energy.12. The method of wherein the electroporation step comprise delivering the pulse of energy to a plurality of electrodes according to a pulse sequence pattern that delivers the pulse of energy in a decentralized pattern.13. The ...

ROADMAP FOR CONTROLLING MALARIA

Embodiments of the present invention concern methods of preventing malaria in a target population of humans comprising: uniformly administering a therapeutically effective amount of a live low dose malaria vaccine to each individual within the target population on each of two or three consecutive days. The methods include using infected mosquitoes to inject into individuals through mosquito bites. 1. A method of preventing malaria in a target population of humans comprising:uniformly administering a therapeutically effective amount of a live low dose malaria vaccine to each individual within the target population on each of two consecutive days.2. A method of preventing malaria in a human comprising:administering a therapeutically effective amount of a live low dose malaria vaccine to the human on each of two consecutive days.3. A method of preventing malaria in a target population of humans comprising:uniformly administering a therapeutically effective amount of a live low dose malaria vaccine to each individual within the target population on each of three consecutive days.4. The method of further comprising administering the therapeutically effective amount of a live low dose malaria vaccine to the human on a third consecutive day.5Plasmodium.. The method of wherein the live low dose malaria vaccine contains a drug sensitive strain of6Plasmodium. The method of wherein the malaria vaccine consists of a plurality of drug sensitive infected mosquitoes in a container and the administration of the vaccine consists of allowing each individual human in the target population to be exposed to the mosquitoes in the container and receive at least five mosquito bites therefrom.7Plasmodium. The method of wherein the drug to which the is sensitive is chloroquine or mefloquine.8. The method of wherein the drug sensitive live organisms are drug sensitive due to loss of a non-chromosomal resistance gene.9Plasmodium.. The method of wherein the live low dose malaria vaccine ...

MALARIA VACCINES BASED ON PRE-ERYTHROCYTIC ANTIGENS FROM P. FALCIPARUM

The present invention relates to polypeptides or fragments thereof for use as malaria vaccines. It also relates to nucleic acid molecules coding for the polypeptides of the invention. It further relates to compositions comprising such polypeptides or fragments thereof or the nucleic acid molecules, in particular combinations of such polypeptides or fragments thereof, and the use of such compositions as malaria vaccines. 2. (canceled)4. The composition of claim 1 , wherein the at least two polypeptides are selected from polypeptides comprising an amino acid sequence of SEQ ID NOs. 1 to 25 or fragment(s) thereof or a fragment of one of said amino acid sequences.5. The composition of claim 1 , comprising at least three claim 1 , of the polypeptides or fragments of the polypeptides.6. (canceled)8. The composition of claim 1 , wherein the fragment comprises at least one antigenic determinant or epitope of the amino acid sequence.9. The composition of claim 8 , wherein the antigenic determinant or epitope is a CD8+ T cell epitope claim 8 , a CD4+ T cell epitope.11. The composition of claim 10 , comprising at least one fragment comprising an amino acid sequence selected fromSEQ ID NOs. 26 to 28,SEQ ID NOs. 29 and 30,SEQ ID NOs. 31 to 33,SEQ ID NOs. 34 and 35,SEQ ID NO. 36, andSEQ ID NOs. 37 to 40.12. The composition according to claim 1 , wherein the polypeptides or fragments thereof comprise one or more labels claim 1 , N- and/or C-terminal modifications claim 1 , drug(s) or other agents.13. The composition of comprising at least two nucleic acid molecules each encoding at least one polypeptide claim 1 , or fragment thereof claim 1 , according to .14. The composition of claim 13 , comprising at least three of the nucleic acid molecules.15. The composition according to claim 1 , further comprising a carrier and/or an adjuvant.16. The composition of claim 15 , wherein the carrier is a virus particle or a part thereof claim 15 , an envelope protein of a viral vector or of a ...

TREATMENT AND PREVENTION OF MALARIA

The present invention relates to polypeptides from and polynucleotides encoding the polypeptides. The invention further relates to compositions comprising the polypeptides and their use in the treatment and prevention of malaria. 1. A composition comprising an isolated and/or recombinant polypeptide , wherein the polypeptide comprises:i) an amino acid sequence selected from any one of SEQ ID NOs:2 to 4,ii) an amino acid sequence which is at least 70% identical to any one or more of SEQ ID NOs:2 to 4, and/oriii) an antigenic fragment of i) or ii).2. The composition of claim 1 , wherein the polypeptide comprises an amino acid sequence which is at least 90% identical to any one or more of SEQ ID NOs:2 to 4 or an antigenic fragment thereof.3. The composition of claim 1 , wherein the composition further comprises an Rh polypeptide or antigenic fragment thereof.4. The composition of claim 3 , wherein the Rh polypeptide or antigenic fragment comprises:i) an amino acid sequence selected from any one of SEQ ID NOs:10 to 28,ii) an amino acid sequence which is at least 70% identical to any one or more of SEQ ID NOs:10 to 28, and/oriii) an antigenic fragment of i) or ii).5. The composition of which comprises an Rh1 polypeptide or antigenic fragment thereof claim 3 , and which comprises:i) an amino acid sequence as set forth in SEQ ID NO:10,ii) an amino acid sequence which is at least 70% identical to SEQ ID NO:10, and/oriii) an antigenic fragment of i) or ii).6. The composition of which comprises an Rh2 polypeptide or antigenic fragment thereof claim 3 , and which comprises:i) an amino acid sequence selected from any one of SEQ ID NOs:11 to 14,ii) an amino acid sequence which is at least 70% identical to any one or more of SEQ ID NOs:11 to 14, and/oriii) an antigenic fragment of i) or ii).7. The composition of which comprises an Rh4 polypeptide or antigenic fragment thereof claim 3 , and which comprises:i) an amino acid sequence as set forth in SEQ ID NO:15 or SEQ ID NO:16,ii) ...

Methods and Compositions for Preventing a Condition

Provided herein are methods, compositions, and kits for preventing, inhibiting, reducing the severity of, or treating a disease or condition. A pharmaceutical composition provided herein can comprise a nucleic acid sequence encoding an antigen fused to an immune cell product, e.g., MIP-3α, and an adjuvant. The antigen can be from a bacteria, virus, fungus, parasite, or cancer. The antigen can be an Alzheimer's disease antigen. 1. A pharmaceutical composition comprising:a. a nucleic acid sequence encoding an antigen or a fragment thereof fused to macrophage inflammatory protein 3 alpha or a fragment thereof; andb. an adjuvant.298-. (canceled) This application is a continuation of U.S. application Ser. No. 13/206,471, filed on Aug. 9, 2011, which claims the benefit of U.S. Provisional Applications Nos. 61/371,923, filed Aug. 9, 2010, and 61/466,175, filed Mar. 22, 2011, all of which are incorporated herein by reference in their entireties.This invention was made with the support of the United States government under Grant number R21AI073619 by National Institutes of Health. The government has certain rights in the invention.Vaccines play a role in the prevention and treatment of diseases, including cancer and infections. For some conditions, e.g., malaria, few effective vaccines are available. Vaccine studies using irradiated sporozoites have demonstrated the theoretical feasibility of an effective vaccine to protect against the pre-erythrocytic stages of malaria infection. Subsequent studies have shown that the protection observed in murine model systems of malaria can involve both humoral and cell-mediated immunity, but can depend on the activity of T lymphocytes, presumably due to the need to destroy infected cells within the liver. Although interest persists in the use of irradiated sporozoites as a malaria vaccine, the feasibility of this approach remains to be established.DNA vaccines can be used to treat a variety of conditions. DNA vaccines can target ...

PROCESS FOR PURIFYING RECOMBINANT PLASMODIUM FALCIPARUM CIRCUMSPOROZOITE PROTEIN

The present invention relates to processes for purifying high-quality recombinant circumsporozoite protein at high yields. 2. The process of claim 1 , further comprising:{'i': 'P. falciparum', '(e) separating the recombinant circumsporozoite protein obtained in step (d) from host cell proteins.'}3P. falciparum. The method of claim 1 , wherein the purified recombinant circumsporozoite protein is obtained at an overall purification yield of about 10% to about 75%.4P. falciparum. The process of claim 3 , wherein recombinant circumsporozoite protein is obtained at an overall purification yield of: about 10% to about 75% claim 3 , about 10% to about 70% claim 3 , about 10% to about 60% claim 3 , about 10% to about 50% claim 3 , about 10% to about 40% claim 3 , about 10% to about 30% claim 3 , about 20% to about 75% claim 3 , about 20% to about 50% claim 3 , about 20% to about 40% claim 3 , or about 20% to about 30%.5P. falciparum. The process of claim 1 , wherein not more than about 10% of the purified recombinant circumsporozoite protein obtained is degraded at the N-terminus.6P. falciparum. The process of claim 1 , wherein not more than about 10% of the purified recombinant circumsporozoite protein obtained is dimerized.7P. falciparum. The process of claim 1 , wherein not more than about 5% of the purified recombinant circumsporozoite protein obtained is present as high molecular weight aggregates.8P. falciparum. The process of claim 1 , wherein not more than about 10% of the purified recombinant circumsporozoite protein obtained is denatured.9P. falciparumP. falciparum. The process of claim 1 , wherein the purified recombinant circumsporozoite protein obtained comprises at least about 90% circumsporozoite protein monomer.10. The process of claim 1 , wherein the bacterial cell lysate is a Pseudomonad cell lysate.11Pseudomonas. The process of claim 10 , wherein the Pseudomonad cells are cells.12PseudomonasPseudomonas fluorescens.. The process of claim 11 , wherein the ...

IMMUNOGENIC COMPOSITIONS AND EXPRESSION SYSTEMS

Immunogenic compositions and vaccines against Plasmodial infection comprising an Rh polypeptide or a fragment or variant thereof are disclosed. Also disclosed are Rh5 polypeptides or fragments or variants thereof capable of binding CD147 and conferring protection against infection and/or disease caused by multiple Plasmodial strains or Plasmodial species, inhibitors of the interaction between Rh5 and CD147 and methods for producing polypeptides in a mammalian expression system. 16-. (canceled)7. An inhibitor of the interaction between Rh5 and CD147.8Plasmodium. An inhibitor of the interaction of Rh5 and CD147 for the prevention and or treatment of infection and or disease.9Plasmodium. Use of the inhibitor of the interaction of Rh5 and CD147 in the preparation of a medicament for prevention and or treatment of infection and/or malarial disease.10. An inhibitor or use according to any one of to which is an antibody or fragment or derivative thereof which binds to CD147 , preferably wherein the antibody is Metuximab.11. An inhibitor or use according to according to any one of to which is a soluble fragment of Rh5.12. An inhibitor or use according to any one of to which is an antibody or fragment or derivative thereof which binds to Rh5.13. An inhibitor according to any one of to which is a nucleic acid aptamer or peptide aptamer capable of binding to CD147 or Rh5.14. A method for producing a polypeptide , the method comprising expression of nucleic acid encoding the polypeptide in a eukaryotic cell , and optionally purification of the polypeptide so expressed , wherein:(i) optionally the expressed polypeptide is not N-glycosylated in the cell(ii) the nucleic acid encodes an exogenous eukaryotic signal sequence effective to deliver the polypeptide into the secretory pathway of the eukaryotic cell; and(iii) the nucleic acid has been codon optimised for expression of the polypeptide in the eukaryotic cell.15. A polypeptide produced according to .16Plasmodium. A ...

COMPOSITIONS AND METHODS OF ENHANCING IMMUNE RESPONSES TO EIMERIA OR LIMITING EIMERIA INFECTION

Vaccine vectors and methods of using the vaccine vectors to enhance the immune response to an Apicomplexan parasite and reduce the morbidity or morality associated with subsequent infection are provided herein. The vaccine vectors include a polynucleotide encoding a Rhomboid polypeptide and optionally include an immune-stimulatory polypeptide suitably expressed on the surface of the vaccine vector. 1. A vaccine vector comprising a first polynucleotide sequence encoding an Apicomplexan Rhomboid polypeptide optionally expressed on the surface of the vaccine vector , wherein the Rhomboid polypeptide consists of a polypeptide having greater than 90% sequence identity to a polypeptide selected from the group consisting of SEQ ID NO: 1 , SEQ ID NO: 2 , SEQ ID NO: 3 , SEQ ID NO: 4 , SEQ ID NO: 37 , SEQ ID NO: 38 , an immunogenic fragment of SEQ ID NO: 1 , an immunogenic fragment of SEQ ID NO: 2 , an immunogenic fragment of SEQ ID NO: 3 , an immunogenic fragment of SEQ ID NO: 4 , an immunogenic fragment of SEQ ID NO: 37 , an immunogenic fragment of SEQ ID NO: 38 and combinations thereof.2. The vaccine vector of claim 1 , further comprising a second polynucleotide sequence encoding an immunostimulatory polypeptide claim 1 , wherein the immunostimulatory polypeptide is expressed on the surface of the vaccine vector.3. The vaccine vector of claim 2 , wherein the immunostimulatory polypeptide comprises an HMGB1 polypeptide.4. The vaccine vector of claim 3 , wherein the HMGB1 polypeptide comprises a polypeptide selected from the group consisting of SEQ ID NOs: 15-23 claim 3 , a fragment of at least one of SEQ ID NOs: 15-23 claim 3 , a polypeptide having at least 95% sequence identity to SEQ ID NO: 15-23 and combinations thereof.5. The vaccine vector of claim 2 , wherein the immunostimulatory polypeptide comprises a CD154 polypeptide capable of binding CD40 claim 2 , the CD154 polypeptide having fewer than 50 amino acids and comprising amino acids 140-149 of a polypeptide ...

PD-1 Peptide Inhibitors

This disclosure provides peptides which have a strong affinity for the checkpoint receptor “programmed death 1” (PD-1). These peptides block the interaction of PD-1 with its ligand PD-L1 and can therefore be used for various therapeutic purposes, such as inhibiting the progression of a hyperproliferative disorder, including cancer, treating infectious diseases, enhancing a response to vaccination, and treating sepsis. 1. A method of inhibiting progression of a hyperproliferative disorder , to treat an infectious disease , or to treat sepsis , comprising administering to a patient in need thereof an effective amount of a pharmaceutical composition comprising: (i) a peptide consisting of the amino acid sequence SEQ ID NO:1;', '(ii) a peptide consisting of the amino acid sequence SEQ ID NO:2;', '(iii) a peptide consisting of the amino acid sequence SEQ ID NO:3; and', '(iv) a peptide consisting of the amino acid sequence SEQ ID NO:4; and, '(a) up to four peptides selected from the group consisting of(b) a pharmaceutically acceptable vehicle.2. The method of claim 1 , wherein the composition is administered to inhibit progression of a hyperproliferative disorder.3. The method of claim 2 , wherein the hyperproliferative disorder is a cancer.4. The method of claim 3 , wherein the cancer is a melanoma.5. The method of claim 3 , further comprising administering a cancer vaccine to the patient.6. The method of claim 2 , further comprising administering a chimeric antigen receptor (CAR) T cell therapy to the patient.7. The method of claim 1 , wherein the composition is administered to treat an infectious disease.8. The method of claim 7 , wherein the infectious disease is malaria.9. The method of claim 7 , wherein the infectious disease is hepatitis B.10. The method of claim 7 , wherein the composition is administered as a vaccine adjuvant to a vaccine against the infectious disease.11. The method of claim 1 , wherein the composition is administered to treat sepsis.12. The ...

Anti-Malarial Compositions

This disclosure provides antibodies that are useful for preventing and/or treating malaria. The epitope to which the antibodies bind is in close proximity to the conserved proteolytic cleavage site of circumsporozoite protein (CSP), and the antibodies provided in this disclosure can prevent cleavage and inhibit sporozoites from invading the liver. 1. A method of producing a heavy chain of an antibody , comprising growing a host cell comprising a gene expression construct encoding the heavy chain under conditions which permit expression of the gene expression construct , wherein the gene expression construct comprises a coding sequence for the heavy chain , wherein the variable region of the heavy chain comprises:{'sub': H', 'H', 'H, '(i) a first heavy chain complementarity determining region (CDR) comprising the amino acid sequence SEQ ID NO:1; a second CDRcomprising the amino acid sequence SEQ ID NO:2; and a third CDRcomprising the amino acid sequence SEQ ID NO:3; or'}(ii) the complementarity determining regions of the heavy chain variable region of the antibody deposited under Accession No. MRA-1242.2. The method of claim 1 , wherein the variable region comprises the first CDRcomprising the amino acid sequence SEQ ID NO:1; the second CDRcomprising the amino acid sequence SEQ ID NO:2; and the third CDRcomprising the amino acid sequence SEQ ID NO:3.3. The method of claim 1 , wherein the variable region comprises the CDRs of the heavy chain of the antibody deposited under Accession No. MRA-1242.4. A method of producing a light chain of an antibody claim 1 , comprising growing a host cell comprising a gene expression construct encoding the light chain under conditions which permit expression of the gene expression construct claim 1 , wherein the gene expression construct comprises a coding sequence for the light chain claim 1 , wherein the variable region of the light chain comprises:{'sub': L', 'L', 'L, '(i) a first CDRcomprising the amino acid sequence SEQ ID NO:4; ...

TARGETING OF CHONDROITIN SULFATE GLYCANS

The present invention relates to functional binding fragments comprising the minimal binding fragments of VAR2CSA, to antibodies against such binding fragments of VAR2CSA, nucleic acids encoding such fragments of VAR2CSA as well as methods for their production. The invention further relates to conjugates and fusion proteins of VAR2CSA polypeptides including the minimal binding fragments and their use, in particular in the treatment of conditions associated with expression of chondroitin sulfate A (CSA), such as an inappropriate expression of chondroitin sulfate A (CSA). 117-. (canceled)18. A conjugate or fusion protein comprising a VAR2CSA polypeptide , and a therapeutic or diagnostic effector moiety , such as a cytotoxic moiety , fluorescent label , and/or a radio label.19. The conjugate according to claim 18 , wherein the VAR2CSA polypeptide is or comprises a protein fragment consisting of a sequential amino acid sequence ofa) ID1, andb) DBL2Xb, and optionally ID2a.20Pseudomonas. The conjugate according to claim 18 , wherein the cytotoxic moiety is selected from calicheamycin claim 18 , auristatin claim 18 , doxorubicin claim 18 , maytansinoid claim 18 , taxol claim 18 , ecteinascidin claim 18 , geldanamycin claim 18 , methotrexate and their derivatives claim 18 , cytotoxic proteins such as exotoxin A claim 18 , diphtheria toxin claim 18 , ricin toxin claim 18 , pokeweed antiviral protein claim 18 , saporin claim 18 , gelonin and functional variants claim 18 , fragments claim 18 , and combinations thereof.2122-. (canceled)23. The conjugate according to claim 18 , wherein the therapeutic or diagnostic effector moiety is an anti-inflammatory agent.24. The conjugate according to claim 18 , wherein the therapeutic or diagnostic effector moiety is CSPG4 claim 18 , CD44 claim 18 , or other proteoglycans exemplified but not limited to those in Table 1.25. A composition comprising the conjugate according to .2632-. (canceled)33. A method for the treatment of any ...

COMPOSITIONS AND METHODS OF ENHANCING IMMUNE RESPONSES TO EIMERIA OR LIMITING EIMERIA INFECTION

Vaccine, vectors and methods of using the vaccine vectors to enhance the immune response to an Apicomplexan parasite and reduce the morbidity or mortality associated with subsequent infection are provided herein. The vaccine vectors include a polynucleotide encoding a Rhomboid polypeptide and optionally include an immune-stimulatory polypeptide suitably expressed on the surface of the vaccine vector. 1. A vaccine vector comprising a first polynucleotide sequence encoding an Apicomplexan Rhomboid polypeptide expressed on the surface of the vaccine vector , wherein the Rhomboid polypeptide consists of a polypeptide having greater than 90% sequence identity to a polypeptide having the amino acid sequence selected from the group consisting of SEQ ID NO: 3 , SEQ ID NO: 4 , an immunogenic fragment of SEQ ID NO: 3 , an immunogenic fragment of SEQ ID NO: 4 , and combinations thereof.2. The vaccine vector of claim 1 , further comprising a second polynucleotide sequence encoding an immunostimulatory polypeptide claim 1 , wherein the immunostimulatory polypeptide is expressed on the surface of the vaccine vector claim 1 , and wherein an immunostimulatory polypeptide comprises a polypeptide capable of stimulating an immune response.3. The vaccine vector of claim 2 , wherein the immunostimulatory polypeptide comprises an HMGB1 polypeptide.4. The vaccine vector of claim 3 , wherein the HMGB1 polypeptide comprises a polypeptide selected from the group consisting of SEQ ID NOs: 15-23 a polypeptide having at least 95% sequence identity to SEQ ID NO: 15-23 and combinations thereof.5. The vaccine vector of claim 2 , wherein the immunostimulatory polypeptide comprises a CD154 polypeptide capable of binding CD40 claim 2 , the CD154 polypeptide having fewer than 50 amino acids and comprising amino acids 140-149 of a polypeptide selected from the group consisting of SEQ ID NO: 24 claim 2 , SEQ ID NO: 25 claim 2 , SEQ ID NO: 26 claim 2 , SEQ ID NO: 27 claim 2 , SEQ ID NO: 28 claim 2 , SEQ ...

PLASMODIAL SURFACE ANION CHANNEL INHIBITORS FOR THE TREATMENT OR PREVENTION OF MALARIA

The invention provides methods of treating or preventing malaria comprising administering to an animal an effective amount of a compound of formula I: 1. A method of treating or preventing malaria in an animal comprising administering an effective amount of a compound of formula (I) to the animal:{'br': None, 'sup': 1', '2, 'Q—Y—R—R\u2003\u2003(I),'}wherein:Q is selected from the group consisting of a dioxo heterocyclyl ring fused to an aryl group, a heterocyclic amido group linked to a heterocyclic group, alkyl, a heterocyclic group fused to a heterocyclic amido group, arylamino carbonyl, amino, heterocyclic amido, and heterocyclic amino group, each of which, other than amino, is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxy, mercapto, alkoxy, alkylthio, nitro, cyano, amino, alkyl, aryl, hydroxyalkyl, haloalkyl, cyanoalkyl, aminoalkyl, alkylamino, dialkylamino, carboxy, carboxyalkyl, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, ureido, and formyl;{'sub': '2', 'Y is a bond, S, SO, or amido;'}{'sup': '1', 'Ris divalent group selected from the group consisting of a heterocyclic ring having at least one nitrogen atom, piperidinyl, piperazinyl, aryl, a heterocyclic ring having at least one nitrogen atom linked to an alkylamino group, benzo fused heterocyclyl, heterocyclyl fused to an iminotetrahydropyrimidino group, and heterocyclyl fused to a heterocyclic amido group, each of which is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxy, mercapto, alkoxy, alkylthio, nitro, cyano, amino, alkyl, hydroxyalkyl, haloalkyl, cyanoalkyl, aminoalkyl, alkylamino, dialkylamino, carboxy, carboxyalkyl, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, ureido, and formyl;'}{'sup': '2', 'Ris selected from the group consisting of arylalkenyl, heterocyclyl carbonylamino, heterocyclyl alkylamino, tetrahydroquinolinyl alkenyl, tetrahydroisoquinolinyl alkyl, indolylalkenyl, ...

RNA FOR MALARIA VACCINES

The present invention is directed to a coding RNA for a Malaria vaccine. The coding RNA comprises at least one heterologous untranslated region (UTR), preferably a 3′-UTR and/or a 5′-UTR, and a coding region encoding at least one antigenic peptide or protein derived from a Malaria parasite, in particular at least one antigenic protein derived from circumsporozoite protein (CSP) of a Malaria parasite (e.g. ). The present invention is also directed to compositions and vaccines comprising said coding RNA in association with a polymeric carrier, a polycationic protein or peptide, or a lipid nanoparticle (LNP). Further, the invention concerns a kit, particularly a kit of parts comprising the coding RNA, or the composition, or the vaccine. The invention is also directed to a method of treating or preventing Malaria, and the first and second medical uses of the coding RNA, the composition, the vaccine, and the kit. 1. A coding RNA for a vaccine comprisinga) at least one heterologous 5′ untranslated region (5′-UTR) and/or at least one heterologous 3′ untranslated region (3′-UTR); andb) at least one coding sequence operably linked to said 3′-UTR and/or 5′-UTR encoding at least one antigenic protein derived from circumsporozoite protein (CSP) of a Malaria parasite, or an immunogenic fragment or immunogenic variant thereof:2Plasmodium falciparumPlasmodium knowlesiPlasmodium ovalePlasmodium simiovalePlasmodium vivax. Coding RNA of claim 1 , wherein the Malaria parasite is selected from (Pf) claim 1 , (Pk) claim 1 , (Po) claim 1 , (Ps) claim 1 , or (Pv).3Plasmodium falciparumPlasmodium falciparum. Coding RNA of or claim 1 , wherein the Malaria parasite is (Pf) claim 1 , preferably 3D7.4. Coding RNA of any one of to claim 1 , wherein the coding sequence additionally encodes at least one heterologous peptide or protein element selected from a heterologous signal peptide claim 1 , a linker claim 1 , a helper epitope claim 1 , an antigen clustering domain claim 1 , or a ...

VIRUS LIKE PARTICLE WITH EFFICIENT EPITOPE DISPLAY

The invention relates to a virus like particle (VLP) based vaccine. The virus-like particle constitutes a non-naturally occurring, ordered and repetitive antigen array display scaffold which can obtain a strong and long-lasting immune response in a subject. The VLP based vaccine may be used for the prophylaxis and/or treatment of a disease including, but is not limited to, cancer, cardiovascular, infectious, asthma, and/or allergy diseases/disorders. 1. A vaccine comprising:i. a papilloma virus (PV) L1 protein containing a biotin acceptor site, andii. a biotin molecule enzymatically conjugated to said biotin acceptor site, andiii. an antigen fused to a monovalent streptavidin,wherein the antigen and PV L1 protein are linked via the interaction between the monovalent streptavidin and the biotin molecule enzymatically conjugated to the biotin acceptor site of the PV L1 protein, and wherein i-iii form a virus like particle displaying said antigen.27.-. (canceled)8. The vaccine according to claim 1 , wherein the PV L1 protein is from a virus infecting mammals.9. The vaccine according to claim 1 , wherein the PV L1 protein is from the human PV genotype 16 and/or 118.10. The vaccine according to claim 1 , wherein the biotin acceptor site comprises amino acid sequence SEQ ID NO: 36.11. The vaccine according to claim 1 , wherein the biotin acceptor site is fused into a loop of the PV L1 protein claim 1 , the loop selected from the group consisting of: a DE-loop and an HI-loop of the PV L1 protein.12. The vaccine according to claim 1 , wherein the PV L1 protein containing the biotin acceptor site is a PV L1 protein derived from the human PV genotype 16 claim 1 , the PV 1 protein containing the biotin acceptor site having a PV L1 amino acid sequence wherein residues 134-137 (YAAN) are deleted compared to a wild-type PV L1 amino acid sequence claim 1 , and wherein the PV L1 protein contains the biotin acceptor site in a DE-loop at position 133/138 in the amino acid sequence of ...

VACCINE FOR FALCIPARUM MALARIA

The invention provides compositions and methods for preventing or reducing the severity of malaria. 1. A vaccine for reducing the severity of malaria or immunizing against malaria comprising a composition , wherein said composition comprises a purified PfGARP polypeptide antigen comprising the amino acid sequence of PfGARP (SEQ ID NO: 27) or a fragment thereof , said fragment thereof comprising the amino acid sequence of PfGARP (SEQ ID NO: 26) , further comprising an adjuvant.2. The vaccine of claim 1 , wherein said composition comprises a purified polypeptide comprising the amino acid sequence of SEQ ID NO: 26.3. The vaccine of claim 1 , wherein said composition further comprises a purified polypeptide comprising the amino acid sequence of CDPK5 (SEQ ID NO: 47) claim 1 , SERA5 (SEQ ID NO: 70 claim 1 , 72) claim 1 , PfSUB1 (SEQ ID NO: 74) claim 1 , or PfPKG (SEQ ID NO: 76).4. The vaccine of claim 1 , wherein said composition comprises a purified polypeptide that elicits an antibody immune response against PfGARP.5. The vaccine of claim 1 , wherein said composition comprises a purified anti-PfGARP antibody or antigen binding fragment thereof.6. The vaccine of claim 1 , wherein said antibody binds to an antigen comprising a polypeptide having at least 70% identity with an amino acid sequence of SEQ ID NO: 26 or 27 or a fragment thereof.7. The vaccine of claim 1 , wherein said composition further comprises a purified polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 10 claim 1 , 14 claim 1 , 18 claim 1 , 22 claim 1 , 30 claim 1 , 34 claim 1 , 38 claim 1 , 42 claim 1 , 46 claim 1 , 66 and 72.8. The vaccine of claim 1 , wherein said composition further comprises a purified polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 8 claim 1 , 11 claim 1 , 15 claim 1 , 19 claim 1 , 22 claim 1 , 31 claim 1 , 35 claim 1 , 39 claim 1 , 43 claim 1 , 47 claim 1 , 67 claim 1 , 70 claim 1 , 74 claim ...

Anti-PfRH5 Antibodies and Antigen-Binding Fragments Thereof

The present invention includes antibodies and antigen-binding fragments thereof that specifically bind to reticulocyte binding protein homologue 5 (PfRH5), compositions thereof and methods of making such antibodies, fragments and compositions. Method and compositions for treating, preventing or diagnosing infection and malaria are also part of the present invention. 1. An antigen-binding protein that{'i': 'Plasmodium Falciparum', '(i) specifically binds to the same epitope on reticulocyte binding protein homologue 5 (PfRH5) polypeptide as a reference antigen-binding protein; or'}(ii) competes for binding to PfRH5 polypeptide with a reference antigen-binding protein wherein the reference antigen-binding protein comprises:(a) a heavy chain immunoglobulin that comprises CDR-H1, CDR-H2 and CDR-H3 of a heavy chain immunoglobulin that comprises the amino acid sequence set forth in SEQ ID NO: 2, 18, 34, 50, 66, 82, 98, 114, 130, 146, 162, 178, 194, 210, 226, 234, 242, 250, 258, 266, 274, 282, 290, 298, 314, 322, 330, 338, 346 or 354; and/or(b) a light chain immunoglobulin that comprises CDR-L1, CDR-L2 and CDR-L3 of a light chain immunoglobulin that comprises the amino acid sequence set forth in SEQ ID NO: 10, 26, 42, 58, 74, 90, 106, 122, 138, 154, 170, 186, 202, 218 or 306.2. The antigen-binding protein of comprising:(i) a heavy chain immunoglobulin variable region that comprises CDR-H1, CDR-H2 and CDR-H3 of a heavy chain immunoglobulin variable region that comprises the amino acid sequence set forth in SEQ ID NO2, 18, 34, 50, 66, 82, 98, 114, 130, 146, 162, 178, 194, 210, 226, 234, 242, 250, 258, 266, 274, 282, 290, 298, 314, 322, 330, 338, 346 or 354; and/or(ii) a light chain immunoglobulin variable region that comprises CDR-L1, CDR-L2 and CDR-L3 of a light chain immunoglobulin variable region that comprises the amino acid sequence set forth in SEQ ID NO: 10, 26, 42, 58, 74, 90, 106, 122, 138, 154, 170, 186, 202, 218 or 306.3. The antigen-binding protein of any one of - ...

ANTIGENIC COMPOSITIONS AND METHODS

Multilayer films comprised of polypeptide epitopes and a toll-like receptor ligand. The multilayer films are capable of eliciting an immune response in a host upon administration to the host. The multilayer films can include at least one designed peptide that includes one or more polypeptide epitopes from a virus, bacteria, fungus or parasite. 1. A composition comprisinga first multilayer film comprising a plurality of oppositely charged polyelectrolyte layers, wherein one of the polyelectrolyte layers in the multilayer film comprises a first antigenic polyelectrolyte, wherein the first antigenic polyelectrolyte comprises a viral, bacterial, fungal or parasite polypeptide epitope,wherein the multilayer film comprises a toll-like receptor ligand, andwherein the polyelectrolytes in the multilayer film comprise a polycationic material or a polyanionic material having a molecular weight of greater than 1,000 and at least 5 charges per molecule.2. The composition of wherein the first antigenic polyelectrolyte is a polypeptide.3. The composition of claim 1 , wherein the TLR ligand is covalently linked to the first antigenic polyelectrolyte.4. The composition of claim 1 , wherein the first multilayer film is deposited on a core particle.5. The composition of claim 1 , wherein the toll-like receptor ligand is covalently attached to a second polyelectrolyte in the multilayer film.6. The composition of claim 1 , wherein the toll-like receptor ligand is not covalently attached to a polyelectrolyte and is codeposited with one of the polyelectrolyte layers of the multilayer film.7. The composition of claim 1 , further comprising a second multilayer film comprising a plurality of oppositely charged polyelectrolyte layers claim 1 , wherein one of the layers in the second multilayer film comprises a second antigenic polyelectrolyte claim 1 ,wherein the second antigenic polyelectrolyte comprises a viral, bacterial, fungal or parasite polypeptide epitope, wherein the first and second ...

COMPOSITION AND USES THEREOF

The present invention provides a particle comprising a fusion protein, wherein the fusion protein comprises at least one NANP repeat (SEQ ID NO: 7), some or all of the C-terminus of the CS protein from and a hepatitis B surface antigen, and wherein the particle comprises no, or substantially no, free hepatitis B surface antigen protein, and uses thereof. 1Plasmodium falciparumPlasmodium falciparum. A method of immunizing a subject against malaria/infection comprising administering to the subject an effective amount of a pharmaceutical composition or vaccine composition , the composition comprising (i) a fusion protein comprising at least one NANP repeat (SEQ ID NO: 7) , some or all of the C-terminus of the CS protein from and a hepatitis B surface antigen; and optionally (ii) a recombinant or non-recombinant modified vaccinia virus Ankara (MVA); and (iii) a pharmaceutically acceptable carrier or excipient.2. The method of claim 1 , wherein the fusion protein and the MVA are administered separately claim 1 , simultaneously claim 1 , or sequentially.3Plasmodium falciparum. A composition comprising (i) a fusion protein comprising at least one NANP repeat (SEQ ID NO: 7) claim 1 , the C-terminus of the CS protein from comprising the sequence: NKNNQGNGQGHNMPNDPNRNVDENANANSAVKNNNNEEPSDKIEKEYLNKIQNSLS TEWSPCSVTCGNGIQVRIKPGSANKPKDELDYANDIEKKICKMEKCSSVFN VVNSSIGI (SEQ ID NO: 6); or the sequence NKNNQGNGQGHNMPNDPNRNVDENANANSAVKNNNNEEPSDKHIKEYLNKIQ NSLSTEWSPCSVTCGNGIQVRIKPGSANKPKDELDYANDIEKKICKMEKCSSV (SEQ ID NO: 4) claim 1 , or a sequence with 90% or more sequence identity therewith claim 1 , and a hepatitis B surface antigen (HBsAg); and optionally (ii) a recombinant or non-recombinant modified vaccinia virus Ankara (MVA).4. The composition of claim 3 , wherein the fusion protein is provided as a virus-like particle claim 3 , the virus-like particle comprising no free HBsAg.5. The composition of claim 3 , wherein the fusion protein is RTS.6. The composition of claim 5 , ...

Recombinantly Expressed Plasmodium CelTOS Antigen and Methods of Use Thereof

A synthetic nucleotide, which transcribes as the cell-traversal protein for ookinetes and sporozoites (CelTOS) antigen of Malaria , and methods of use thereof. 1Plasmodium. A synthetic nucleotide encoding a CelTOS antigen of said nucleotide comprising the nucleotide sequence identified in SEQ ID NO:1 or a substantially homologous sequence thereof.2Plasmodium. The synthetic nucleotide of claim 1 , wherein said CelTOS antigen of the amino acid sequence identified in SEQ ID NO:2 or a substantially homologous sequence thereof.3. A synthetic CelTOS polypeptide claim 1 , said polypeptide encoded by the synthetic nucleotide sequence identified in SEQ ID NO:1 or a substantially homologous sequence thereof.411-. (canceled)12. An immunogenic composition comprising the synthetic CelTOS polypeptide of .1314-. (canceled)15. The synthetic polypeptide of claim 3 , wherein said protein is recombinantly expressed with no post-translational N-glycosylation.1626-. (canceled)27. A recombinant vector comprising the synthetic nucleotide of .28. A host cell transformed with the vector according to .29. The host cell of wherein the host cell is prokaryotic.30E. coli.. The host cell of wherein the host cell is31Plasmodium. A method for isolating and purifying synthetic CelTOS antigen comprising:{'i': 'Plasmodium', 'claim-ref': {'@idref': 'CLM-00027', 'claim 27'}, 'growing a host cell containing a recombinant vector expressing CelTOS antigen according to in a suitable culture medium,'}{'i': 'Plasmodium', 'causing expression of said vector under suitable conditions for production of CelTOS antigen, and'}{'i': 'Plasmodium', 'lysing said host cells and recovering said CelTOS antigen.'}32E. coli. The method of further comprising removal of proteins.33. The immunogenic composition of further comprising an adjuvant.34. A malaria vaccine comprising the synthetic CelTOS polypeptide of .35. The vaccine of further comprising an adjuvant.36Plasmodium. A method for inducing an immune response to malaria ...

A MALARIA VACCINE AND METHODS FOR PRODUCING SAME

The present description relates to malaria vaccines comprising (Pf) polypeptide complexes and methods of producing the same. The Pf polypeptides in complexes or in a partially complexed arrangement may comprise two or more of the following polypeptides: PfRipr, PfCyrPa and PfRh5. cells and expression vectors are also described. 1DrosophilaPlasmodium falciparum. A derived cell modified to express a (Pf) Ripr polypeptide from a heterologous polynucleotide encoding a PfRipr polypeptide and a suitable signal sequence , wherein the polynucleotide is operably linked to an expression control sequence which induces PfRipr polypeptide expression in the cell and wherein the PfRipr polypeptide from said cell induces merozoite invasion inhibitory antibodies when administered to a subject.2. The cell of further comprising one or more of:(a) a heterologous polynucleotide encoding PfRh5 polypeptide and a suitable signal sequence, operably linked to an expression control sequence which induces PfRh5 polypeptide expression in the cell wherein co-expression of PfRipr and PfRh5 polypeptides in the cell induces increased yields of either or both polypeptides compared to mono-expression of either polypeptide;(b) a heterologous polynucleotide encoding a PfCyrPa polypeptide and a suitable signal sequence, operably linked to an expression control sequence which induces PfCyrPa polypeptide expression in the cell; or(c) a heterologous polynucleotide encoding a PfEBA175 polypeptide and a suitable signal sequence, operably linked to a promoter which induces EBA175 polypeptide expression in the cell.3. (canceled)4. (canceled)5DrosophilaPlasmodium falciparumDrosophila. A derived cell of further modified to express a (Pf) Rh5 polypeptide and a PfCyrPa polypeptide from a heterologous polynucleotide encoding a PfRh5 polypeptide and a suitable signal sequence operably linked to a promoter which induces PfRh5 polypeptide expression and a PfCyrPa polypeptide and a suitable signal sequence operably ...

USES OF PARASITE MACROPHAGE MIGRATION INHIBITORY FACTORS

This invention relates to compositions (e.g. vaccine compositions) which can be used to provide a subject with protective immunity against a parasite infection. The compositions comprise: (i) an immunologically effective amount of a nucleic acid (e.g. a nucleic acid-based vaccine) comprising a sequence which encodes a parasite macrophage migration inhibitory factor (MIF) antigen; (ii) a parasite MIF antigen; or (iii) an antibody which specifically binds to a parasite MIF antigen. The compositions may be used to treat infections and diseases caused by parasitic protozoans, such as a parasite, or parasitic helminths. 1. A composition for use in a method of providing protective immunity against a parasite infection in a subject in need thereof , which comprises an immunologically effective amount of one or more of:(i) a nucleic acid comprising a sequence which encodes a parasite macrophage migration inhibitory factor (MIF) antigen;(ii) a parasite MIF antigen; or(iii) an antibody which specifically binds to a parasite MIF antigen.2. The composition for use according to (i) wherein the composition comprises an RNA-based vaccine.3. The composition for use according to or wherein the protective immunity is characterized by protective immunological memory against the parasite and/or an effective parasite-responsive memory T cell population.4. The composition for use according to claim 1 , or wherein the composition comprises a nucleic acid-based vaccine comprising the nucleic acid sequence which encodes a parasite MIF antigen; for example claim 1 , wherein the nucleic acid-based vaccine is a RNA-based vaccine claim 1 , which may comprises a self-replicating RNA molecule claim 1 , such as an alphavirus-derived RNA replicon.5. The composition for use according to any preceding claim wherein the composition comprises a cationic nano-emulsion (CNE) delivery system or a lipid nanoparticle (LNP) delivery system.6. The composition for use according to any preceding claim wherein ...

NOVEL MALARIA VACCINE

The present invention provides a vaccine for preventing and/or treating infections, which comprises a polypeptide set forth in SEQ ID NO: 1 or represented by formula (1), and an adjuvant. 111-. (canceled)12Plasmodium falciparum. A vaccine for preventing and/or treating a infection , comprising the polypeptide set forth in SEQ ID NO: 1 , and an adjuvant , wherein the adjuvant is a combination of K3 (K-type CpG adjuvant) , with aluminium hydroxide gel.13Plasmodium falciparum. A method for preventing and/or treating a infection by administrating the polypeptide set forth in SEQ ID NO: 1 together with adjuvants wherein the adjuvants are K3 (K-type CpG adjuvant) and aluminium hydroxide gel. The present invention relates to a high-immunogenicity polypeptide that is useful as a malaria vaccine. The present invention relates to a vaccine that is useful for preventing and treating malaria parasite infections, and a diagnostic agent for malaria parasite infections.Infectious diseases annually cause huge human and social damage in developing countries and elsewhere. In particular, malaria parasite infections annually infect 500 million people and cause the death of 2 million to 3 million people; however, no effective vaccine for the prevention of this disease has been developed. Therefore, there is an urgent need to develop a malaria vaccine.However, in spite of many vaccine clinical tests conducted over the past 30 to 40 years, none of the developed vaccines showed efficacy and all efforts for vaccine development have been frustrated. In such circumstances, as a molecule recognized by an antibody having antimalarial activity, SERA (serine repeat antigen) protein was identified in the serum of adults who have acquired protective immunity (see, for example, Non-patent Literature (NPL) 1).Later, the development of vaccines was conducted using recombinant SERA protein as an antigen. However, because the antibody titer of the obtained anti-SERA protein antibody is lower than that ...

PHARMACEUTICAL COMPOSITIONS COMPRISING ATTENUATED PLASMODIUM SPOROZOITES AND GLYCOLIPID ADJUVANTS

Disclosed herein are pharmaceutical compositions comprising sporozoite-stage parasites and compatible glycolipid adjuvants useful in vaccines for preventing or reducing the risk of malaria. In particular, human host range and analogues of α-galactosylceramide (α-GalCer), a ligand for natural killer T (NKT) cells, are combined in pharmaceutical compositions, which are useful as vaccines against malaria. Methods of use are also provided. 2. The pharmaceutical composition of wherein R═(CH)Ph(p-F).3P. falciparum, P. vivax, P. ovale, P. knowlesi, P. malariaeP. yoelii.. The pharmaceutical composition of wherein said species are selected from the group consisting of: claim 1 , and4P. falciparum.. The pharmaceutical composition of wherein said species comprises5. The pharmaceutical composition of wherein said sporozoite-stage parasites are attenuated.7. The method of wherein R═(CH)Ph(p-F).8. The method of wherein said host is a mammalian host.9. The method of wherein said host is a human host.10. The method of wherein said one or more doses comprise no more than 150 claim 6 ,000 sporozoites.11. The method of wherein said one or more doses comprise no more than 50 claim 10 ,000 sporozoites.12. The method of wherein said one or more doses comprise no more than 25 claim 11 ,000 sporozoites.13. The method of wherein the number of doses is no more than 3.14. The method of wherein the number of doses is no more than 2.15. The method of wherein the number of doses is no more than 1.16PlasmodiumP. falciparum, P. vivax, P. ovale, P. knowlesiP. malariae.. The method of wherein said species of said pharmaceutical composition are selected from the group consisting of claim 6 , and17PlasmodiumP. falciparum.. The method of wherein said species of said pharmaceutical composition comprises18. The method of wherein said pharmaceutical composition is administered by a parenteral route chosen from the group consisting of intravenous claim 6 , intramuscular claim 6 , intradermal claim 6 , and ...

SOLUBLE RECOMBINANT PLASMODIUM FALCIPARUM CIRCUMSPOROZOITE PROTEIN, USE IN VACCINES, METHODS OF MAKING AND USES THEREOF

The present invention provides novel nucleotide sequence and other constructs used for expression of novel recombinant circumsporozoite proteins in bacterial cells such as . Processes are provided for producing a soluble recombinant CSP from . Methods to produce a human-grade, highly immunogenic anti-malaria vaccine based on CSP are shown. The novel recombinant circumsporozoite protein by itself or in combination with other malaria antigens or adjuvants can form the basis of an effective malaria vaccine. 123-. (canceled)24. An anti-malaria vaccine comprising:{'i': 'Plasmodium falciparum', 'claim-text': [{'i': 'P. falciparum', 'lacks twenty to twenty-five amino acid residues from the N-terminus of native circumsporozoite protein sequence;'}, {'i': 'P. falciparum', 'has fewer NANP (SEQ ID NO: 13) repeats compared to native circumsporozoite protein sequence; and'}], 'a recombinant circumsporozoite protein (rCSP) that comprises an amino acid sequence thatone or more adjuvants.25. The vaccine of claim 24 , wherein the adjuvant is Montanide ISA 720.26. The vaccine of claim 24 , wherein the vaccine has an endotoxin level less than about 5 endotoxin units per microgram of protein.27. The vaccine of claim 24 , wherein the vaccine comprises less than about 1 ng/ml of bacterial host proteins.28P. falciparum. The vaccine of claim 24 , wherein the vaccine has a protein content claim 24 , and the protein content is greater than 95% recombinant CSP as measured by gel densitometry.29P. falciparum. The vaccine of claim 24 , wherein the protein content is at least about 99% recombinant CSP as measured by gel densitometry.30. A method of eliciting an immune response against malaria in an animal or human comprising administering the vaccine of to the animal or human.31. (canceled)32. The method of or claim 24 , wherein the vaccine is administered intramuscularly.3343-. (canceled)44. The vaccine of claim 24 , wherein the rCSP comprises 18 or 19 NANP (SEQ ID NO: 13) repeats.45. The ...

MALARIA VACCINE

The present invention provides a particle comprising a polypeptide and at least one malaria antigen, and a composition or vaccine comprising thereof, its use in medicine, particularly in the prevention or treatment of malaria infections. 144-. (canceled)45. A virus-like particle comprising a virus structural polypeptide and at least one malaria antigen ,wherein said virus structural polypeptide is a polypeptide derived from alphavirus or flavivirus.46. The virus-like particle according to claim 45 , wherein said virus structural polypeptide is a polypeptide derived from alphavirus.47. The virus-like particle according to claim 45 , wherein said virus structural polypeptide comprises the capsid and/or the envelope proteins E1 and E2.48. The virus-like particle according to claim 47 , wherein said at least one malaria antigen is inserted into E2 of the envelope protein.49. The virus-like particle according to claim 45 , wherein said virus structural polypeptide is a polypeptide derived from Chikungunya virus (CHIKV) or Venezuelan equine encephalitis virus (VEEV).50. The virus-like particle according to claim 45 , wherein said at least one malaria antigen is a fragment derived from the circumsporozoite protein.51. The virus-like particle according to claim 45 , wherein said at least one malaria antigen is an antigen comprising (NPNA)wherein n is from 4 to 30 and/or an antigen comprising (EYLNKIQSLSTEWSPCSVT)wherein y is from 1 to 6.52. The virus-like particle according to claim 49 , wherein said at least one malaria antigen is inserted between 509-510 claim 49 , 510-511 claim 49 , 511-512 claim 49 , 519-520 claim 49 , 529-530 claim 49 , 530-531 or 531-532 of SEQ ID NO: 1 or 2 claim 49 , or between residues 515-516 claim 49 , 516-517 claim 49 , 517-518 claim 49 , 518-519 claim 49 , 519-520 claim 49 , 536-537 claim 49 , 537-538 or 538-539 of SEQ ID NO: 3.53. The virus-like particle according to claim 49 , wherein the particle is Chikungunya virus-like particle consisting ...

Conjugates of plasmodium falciparum surface proteins as malaria vaccines

Conjugates of ookinete surface protein Pfs25 are provided that are efficacious as vaccines against Plasmodium falciparum , the most severe form of malaria. Conjugates of ookinete surface protein Pvs25 for use as a vaccine against Plasmodium vivax are also provided. Methods for preparing the conjugates, which comprise the ookinete surface protein bound onto itself or onto another protein by a linking group, are also provided.

LONG CHAIN ANTIGEN CONTAINING INTEREPITOPE SEQUENCE THAT PROMOTES ANTIGEN PRESENTATION TO T CELLS

A long-chain peptide antigen includes a plurality of epitopes. An interepitope sequence located between two of the plurality of epitopes contains four to ten consecutive tyrosines, threonines, alanines, histidines, glutamines, or asparagines. The killer T-cell recognition epitopes form complexes with MHC class I molecules and are recognized by CD8+ killer T-cells when the complexes are presented on the surfaces of antigen-presenting cells. The helper T-cell recognition epitopes form complexes with MHC class II molecules and are recognized by CD4+ helper T-cells when the complexes are presented on the surfaces of antigen-presenting cells. The peptide is cleaved within the first interepitope sequence upon uptake of the peptide into antigen-presenting cells. The long-chain peptide antigen may be administered to a patient together with a hydrophobized polysaccharide, such as cholesterol-modified pullulan, and/or an adjuvant, such as CpG oligo DNA.

Viral Vector Immunogenic Compositions

There is provided a composition comprising: (a) a modified vaccinia virus ankara (MVA) vector, wherein said MVA vector comprises a nucleic acid sequence encoding an antigen; and (b) an adjuvant comprising a saponin, or an emulsion. There is also provided a composition comprising: (a) an adenovirus vector, wherein said adenovirus vector comprises a nucleic acid sequence encoding an antigen, and wherein the adenovirus is selected from: a group B adenovirus, a group C adenovirus, and a group E adenovirus; and (b) an adjuvant comprising a saponin, or an emulsion; wherein the group B adenovirus is not an adenovirus 35, the group C adenovirus is not Ad5 having an intact E3 gene region, and the group E adenovirus is not an adenovirus C7. Also provided are corresponding uses of the compositions in medicine. 1. A composition comprising:(a) a modified vaccinia virus ankara (MVA) vector, wherein said MVA vector comprises a nucleic acid sequence encoding an antigen; and(b) an adjuvant comprising a saponin, or an emulsion.2. (canceled)3. The composition of claim 1 , wherein the composition further comprises a polypeptide antigen from a pathogenic organism.46-. (canceled)7ChlamydiaMycobacterium tuberculosisMycobacterium bovisMycobacteriaStaphylococcus aureusStreptococcus pneumoniaeStreptococcus pyogenesHaemophilus influenzaeNeisseria meningitides. The composition of claim 1 , wherein the antigen encoded by the nucleic acid sequence is not a sp. antigen claim 1 , wherein the antigen encoded by the nucleic acid is an antigen selected from the group consisting of: a Plasmodia antigen claim 1 , an influenza virus antigen claim 1 , a antigen claim 1 , a antigen claim 1 , a antigen claim 1 , a hepatitis C virus antigen claim 1 , a flavivirus antigen claim 1 , a hepatitis B virus antigen claim 1 , a human immunodeficiency virus antigen claim 1 , a retrovirus antigen claim 1 , a antigen claim 1 , a Staphylococci antigen claim 1 , a antigen claim 1 , a antigen claim 1 , a Streptococci ...

LIPID VESICLE COMPOSITIONS AND METHODS OF USE

The invention provides delivery systems comprised of stabilized multilamellar vesicles, as well as compositions, methods of synthesis, and methods of use thereof. The stabilized multilamellar vesicles comprise terminal-cysteine-bearing antigens or cysteine-modified antigens, at their surface and/or internally. 162-. (canceled)63. A multilamellar lipid vesicle comprising at least one terminal-cysteine-bearing antigen , and having covalent crosslinks between lipid bilayers , wherein at least two lipid bilayers in the multilamellar lipid vesicle are covalently crosslinked to each other through headgroups that react with covalent crosslinkers to form the covalent crosslinks between lipid bilayers , and wherein the terminal-cysteine bearing antigen is a toll-like receptor (TLR) agonist or a microbial antigen.64. The multilamellar lipid vesicle of claim 63 , wherein the TLR agonist is selected from the group consisting of a TLR3 agonist claim 63 , a TLR4 agonist claim 63 , a TLR5 agonist claim 63 , a TLR7 agonist claim 63 , a TLR8 agonist claim 63 , and a TLR9 agonist.65. The multilamellar lipid vesicle of claim 63 , wherein the multilamellar lipid vesicle comprises a TLR4 agonist and a TLR7 agonist.66. The multilamellar lipid vesicle of claim 63 , wherein the multilamellar lipid vesicle comprises a TLR7 agonist and a TLR8 agonist.67. The multilamellar lipid vesicle of claim 65 , wherein TLR4 agonist is a monophosphoryl lipid A (MPLA).68. The multilamellar lipid vesicle of claim 65 , wherein TLR7 agonist is a resiquimod.69. The multilamellar lipid vesicle of claim 66 , wherein TLR7 agonist is a resiquimod.70. The multilamellar lipid vesicle of claim 63 , wherein the multilamellar lipid vesicle comprises a first terminal-cysteine-bearing TLR agonist and a second terminal-cysteine-bearing TLR agonist claim 63 , wherein the first and the second terminal-cysteine-bearing TLR agonists are different.71. The multilamellar lipid vesicle of claim 63 , wherein the TLR agonist is ...

Plasmodium falciparum antigens

The invention relates to antigens, associated with sterile immunity, and methods of their use, in an immunogenic formulation to confer an immune response against . The inventive antigens were identified by their association with sterile immunity against malaria. 1Plasmodium falciparum. An immunogenic composition comprising a nucleic acid sequence expressed by a suitable expression system , wherein said nucleic acid sequence expresses an isolated protein expressed by sporozoites encoded by one or more of the locus selected from the group consisting of PF10925w , PF14_0051 , PFL2140c , PFE1085w , and PF13_0222 , wherein the isolated protein has the amino acid sequence selected from the group consisting of SEQ ID No. 2 , 6 , 24 , 28 , and 36 , and wherein said isolated protein is expressed from a nucleotide sequence , inserted into a suitable expression vector capable of protein expression in a mammal , wherein the nucleotide sequence comprises the nucleotide sequence selected from the group consisting of SEQ ID No. 1 , 5 , 23 , 27 , and 35 , wherein said suitable expression vector is a DNA plasmid or replicating or nonreplicating viral vector.2Plasmodium falciparum. The immunogenic composition of claim 1 , wherein the composition also comprises a nucleic acid sequence expressed by a suitable expression system claim 1 , wherein said nucleic acid sequence expresses isolated proteins expressed by sporozoites encoded by one or more of the loci selected from the group consisting of PFB0285c claim 1 , PFL1620w claim 1 , PF10_0211 claim 1 , PFB0150c claim 1 , PF11_0344 claim 1 , PFE0060w claim 1 , PF08_0034 claim 1 , PF08_0054 claim 1 , PFC0210c claim 1 , PF11_0404 claim 1 , PF13_0201 claim 1 , PFL2505c claim 1 , PF13_0222 claim 1 , and MAL13P1.22 claim 1 , wherein the isolated proteins have the amino acid sequences selected from the group consisting of claim 1 , with the amino acid sequences of SEQ ID No. 4 claim 1 , SEQ ID No. 10 claim 1 , SEQ ID No. 12 claim 1 , SEQ ID No ...

SUBUNIT VACCINE DELIVERY PLATFORM FOR ROBUST HUMORAL AND CELLULAR IMMUNE RESPONSES

The present invention relates to a probiotic cell transformed with a construct suitable to overexpress and display on the surface of the probiotic cell a fusion protein comprising at least a portion of a transport protein coupled to at least a portion of one or more antigenic proteins or peptides. Probiotic-derived vesicles displaying this fusion protein as well as methods of inducing an immune response using the probiotic cells or vesicles are also disclosed. 1. A probiotic cell transformed with a construct suitable to overexpress and display on the surface of the probiotic cell a fusion protein comprising at least a portion of a transport protein coupled to at least a portion of one or more antigenic proteins or peptides.2. The probiotic cell of claim 1 , wherein the probiotic cell is mutated to hyperexpress vesicles containing the fusion protein.3. The probiotic cell of claim 1 , wherein the transport protein is an adhesin claim 1 , immunomodulatory compound claim 1 , protease claim 1 , or toxin.4. The probiotic cell of claim 1 , wherein the transport protein is ClyA.5StreptococcusCandidaBrucellaSalmonellaShigellaPseudomonasBordetellaClostridiumBacillus anthracis, Mycobacterium tuberculosisChlamydiaPlasmodiumTrichomonas. The probiotic cell of claim 1 , wherein the antigenic protein or peptide is derived from pathogenic bacterial claim 1 , fungal or viral organisms claim 1 , species claim 1 , species claim 1 , species claim 1 , species claim 1 , species claim 1 , species claim 1 , species claim 1 , species claim 1 , Norwalk virus claim 1 , claim 1 , human immunodeficiency virus (HIV) claim 1 , species claim 1 , Human Papillomaviruses claim 1 , Influenza virus claim 1 , Paramyxovirus species claim 1 , Herpes virus claim 1 , Cytomegalovirus claim 1 , Varicella-Zoster virus claim 1 , Epstein-Barr virus claim 1 , Hepatitis viruses claim 1 , species claim 1 , species claim 1 , sexually transmitted disease agents claim 1 , viral encephalitis agents claim 1 , protozoan ...

MALARIA ANTIGENS ON THE SURFACE OF ERYTHROCYTES AND MEROZOITES AND PROTECTIVE ANTIBODIES

Provided herein are compositions and methods for treating and preventing malaria. The vaccine of the invention is directed to the protein encoded by the PF3D7_1134300 gene, or fragments of the protein, which are Pf Erythrocyte Membrane and Merozoite Antigenl (PfEMMAI). Exemplary fragments include Fragment 1, Fragment 2, or a C-terminal fragment of PfEMMAI. 1. A vaccine for preventing or reducing the severity of malaria comprising a composition that comprises a purified polypeptide comprising an amino acid sequence of SEQ ID NO: 1 , 3 , 5 or an antigenic fragment thereof or a polynucleotide encoding said polypeptide , wherein said polypeptide is less than 641 amino acids in length.2. The vaccine of claim 1 , wherein said polypeptide is less than 250 amino acids in length.3. The vaccine of claim 1 , wherein said polypeptide is less than 100 amino acids in length.4. The vaccine of claim 1 , wherein said polypeptide is less than 50 amino acids in length.5. The vaccine of claim 1 , wherein said polypeptide consists essentially of an amino acid sequence of SEQ ID NO: 1 claim 1 , 3 claim 1 , 5 or an antigenic fragment thereof.6. The vaccine of claim 1 , wherein said polynucleotide comprises a nucleic acid sequence of SEQ ID NO: 2 claim 1 , 4 claim 1 , 6 or a fragment thereof.7. The vaccine of claim 1 , wherein said composition inhibits parasite invasion and/or growth of parasites in red blood cells.8. The vaccine of claim 1 , wherein said antigenic fragment comprises an amino acid sequence of SEQ ID NO: 7 claim 1 , 8 claim 1 , 9 claim 1 , 10 claim 1 , 11 claim 1 , 12 claim 1 , 13 claim 1 , 14 claim 1 , 15 claim 1 , 16 claim 1 , 17 claim 1 , 18 claim 1 , 19 or 20.9. A vaccine for preventing or reducing the severity of malaria comprising a purified monoclonal antibody that binds to a polypeptide with an amino acid sequences of SEQ ID NO: 1 claim 1 , 3 claim 1 , or 5.10. The vaccine of claim 1 , further comprising an adjuvant.11. The vaccine of claim 1 , further comprising a ...

ANTI-MALARIAL AGENT

The present invention aims to prevent and/or treat malaria using an antimalarial drug comprising, as an active ingredient, a metal chelator represented by the following formula (I), (III), (IV), (V), (VI), or (VII), such as tris(2-pyridylmethyl)amine. 2. The method according to claim 1 , wherein said compound represented by said Formula (IX) is 4′-(4-Pyridyl)-2 claim 1 ,2′:6′ claim 1 ,2″-terpyridine.3. The method according to claim 1 , wherein said metal complex is a zinc complex.5. The method according to claim 4 , wherein said compound represented by said Formula (X) is Bis(2-pyridylmethyl)(6-benzamide-2-pyridylmethyl)amine.6. The method according to claim 4 , wherein said metal complex is a zinc complex. This patent application is a continuation-in-part of copending U.S. patent application Ser. No. 15/847,432, filed on Dec. 19, 2017, which is a continuation-in-part of U.S. patent application Ser. No. 15/110,708, filed on Jul. 8, 2016, now U.S. Pat. No. 9,861,626, which is the U.S. national phase of International Patent Application No. PCT/JP2015/050513, filed Jan. 9, 2015, which claims the benefit of Japanese Patent Application No. 2014-002428, filed on Jan. 9, 2014, which are incorporated by reference in their entireties herein.The present invention relates to an antimalarial drug.Malaria is a protozoan infection whose pathogen is a malaria parasite. Infection with malaria has been found in not less than 100 countries in the world. According to estimation by the World Health Organization (WHO), about 500 million people are infected with malaria per year, and about 1.5 million people die of malaria every year. For treatment of malaria, drugs such as artemisinin, chloroquine, and atovaquone have been used. However, the number of types of the drugs is small compared to drugs for other infections. Moreover, in view of the current situation where malaria parasites resistant to the drugs described above are found, it is clear that development of novel therapeutic and ...

SELF-ASSEMBLING PROTEIN NANOPARTICLES ENCAPSULATING IMMUNOSTIMULATORY NUCLEID ACIDS

The present invention relates to self-assembling protein nanoparticles encapsulating immunostimulatory nucleid acids. Furthermore, the invention relates to the use of such nanoparticles for vaccination. 1. A composition for inducing an immune response in a subject comprising: {'br': None, 'X1-ND1-L1-ND2-Y1\u2003\u2003(I),'}, '(a) A self-assembling protein nanoparticle (SAPN) consisting of a multitude of building blocks of formula (I)'}consisting of a continuous chain comprising a coiled-coil oligomerization domain ND1, a linker L1, a coiled-coil oligomerization domain ND2 and further substituents X1 and Y1, wherein{'sub': 'm', 'ND1 is a coiled-coil oligomerization domain that comprises oligomers (ND1)of m subunits ND1,'}{'sub': 'n', 'ND2 is a coiled-coil oligomerization domain that comprises oligomers (ND2)of n subunits ND2,'}m and n each is a figure between 2 and 10, with the proviso that m is not equal n and not a multiple of n, and n is not a multiple of m,L1 is a peptide linker with an overall positive charge of at least +2 at physiological conditions,X1 is absent or a peptide or protein sequence comprising 1 to 1000 amino acids that may be further substituted.Y1 is absent or a peptide or protein sequence comprising 1 to 1000 amino acids that may be further substituted, {'br': None, 'X2-ND3-L2-ND4-Y2\u2003\u2003(II),'}, 'wherein the multitude of building blocks of formula (I) is optionally co-assembled with a multitude of building blocks of formula (II)'}consisting of a continuous chain comprising a coiled-coil oligomerization domain ND3, a linker L2, a coiled-coil oligomerization domain ND4, and further substituents X2 and Y2, wherein{'sub': 'y', 'ND3 is a coiled-coil oligomerization domain that comprises oligomers (ND3)of y subunits ND3,'}{'sub': 'z', 'ND4 is a coiled-coil oligomerization domain that comprises oligomers (ND4)of z subunits ND4,'}y and z each is a figure between 2 and 10, with the proviso that y is not equal z and not a multiple of z, and z is ...

IMMUNOGENS OBTAINED FROM PLASMODIUM YOELII USING QUANTITATIVE SEQUENCELINKAGE GROUP SELECTION METHOD

Provided herein are immunogenic compositions against , comprising an immunogenic polypeptide. Also provided are methods of immunizing a subject against , methods of eliciting an immune response in a subject against , and methods of identifying parasite genes driving medically important selectable phenotypes. 1Plasmodium. An immunogenic composition against comprising: (i) PY17X_0721800 found in genomic location PyI7X-07-v2: 799,281-800,081 (+) or an ortholog thereof, or', '(ii) PY17X_0720100 found in genomic location PyI7X-07-v2: 727,812-742,672 (+), or', '(iii) PY17X_0721500 found in genomic location Py17X-07-v2: 784,994-791,991 (+),, '(A) all or part of the nucleotide sequence{'i': Plasmodium yoelii', 'Plasmodium falciparum, 'claim-text': (i) PY17X_0721800 or an ortholog thereof,', '(ii) PY17X_0720100 or an ortholog thereof; or', '(iii) PY17X_0721500 or an ortholog thereof,, 'on chromosome 7 of or an ortholog thereof in or (B) a polypeptide encoded by all or part of the nucleotide sequence{'i': 'Plasmodium falciparum.', 'in'}2Plasmodium. An immunogenic composition against comprising an immunogenic polypeptide , wherein the immunogenic polypeptide is encoded by a nucleic acid sequence with at least 75% sequence identity to a sequence selected from the group consisting of: SEQ ID NOs: 7 , 8 ,9 , 10 , 11 , 12 , 19 , 20 , 21 , 22 , 23 , 24 , 31 , 32 , 33 , 34 , 35 , 36 or a fragment thereof.3. The immunogenic composition of claim 2 , wherein the immunogenic polypeptide is encoded by a nucleic acid sequence with at least 80% sequence identity to a sequence selected from the group consisting of: SEQ ID NOs: 7 claim 2 , 8 claim 2 , 9 claim 2 , 10 claim 2 , 11 claim 2 , 12 claim 2 , or a fragment thereof.4. The immunogenic composition of claim 3 , wherein the immunogenic polypeptide is encoded by a nucleic acid sequence with at least 90% sequence identity to a sequence selected from the group consisting of: SEQ ID NOs: 7 claim 3 , 8 claim 3 , 9 claim 3 , 10 claim 3 , 11 ...

COMBINED MEASLES-MALARIA VACCINE

A combined measles-malaria vaccine containing different attenuated recombinant measles-malaria vectors comprising a heterologous nucleic acid encoding several antigens is described. Preferably, it relates to viral vectors that comprise nucleic acids encoding the circumsporozoite (CS) protein of , the merozoite surface protein 1 (MSP-1) of , and its derivatives (p-42; p-83-30-38) in its glycosylated and secreted forms, and apical membrane antigen1 (AMA1) of , in its anchored or secreted form. The viral vector stems from an attenuated measles virus, based on a strain that is used as a vaccine and is efficient in delivering the gene of interest and that binds to and infects the relevant immune cells efficiently. 142-. (canceled)43. A combined measles-malaria vaccine comprising a recombinant measles vaccine virus which express malaria antigens capable of eliciting immune response and protection both against measles and CS malaria.44. The combined measles-malaria vaccine as claimed in claim 43 , wherein the recombinant measles vaccine virus expresses single or different malaria antigens.45. The combined measles-malaria vaccine as claimed in claim 43 , wherein the recombinant measles vaccine virus expresses CS malaria antigen in both anchored and secreted forms.46. The combined measles-malaria vaccine as claimed in claim 43 , wherein the recombinant measles vaccine virus expresses CS malaria antigen in both anchored and secreted forms 3D7 strain and MAD 20 preferably the FCB1 strain.47. The combined measles-malaria vaccine as claimed in claim 43 , wherein the recombinant measles vaccine virus expresses CS malaria antigen in both anchored and secreted forms FCB1 strain.48. The combined measles-malaria vaccine as claimed in claim 43 , wherein the malaria antigen is cloned between P and M or H and L protein of recombinant measles vaccine virus.49. A measles vaccine virus vector comprising the nucleotide sequence of antigen of malaria.50. The vector as claimed in claim 49 , ...

RODENT PLASMODIUM PARASITES AS PLATFORMS FOR A WHOLE-ORGANISM MALARIA VACCINE

A method for inducing protective immunity in a vertebrate host against malaria, by administering to the host a live rodent organism and exploiting its cross-species protection potential. 1Plasmodium. A live rodent organism for use against human malaria.2PlasmodiumPlasmodiumPlasmodium. The use of the live rodent organism according to claim 1 , wherein the rodent organism is genetically engineered to express genes or gene sections of one or more species of human parasites.3PlasmodiumPlasmodiumPlasmodiumP. berghei, P. yoeli, P. vinckeiP. chabaudi.. The use of the live rodent organism according to claim 1 , wherein the rodent organism is any member of the protozoan genus whose natural host is a rodent claim 1 , including and4Plasmodium. The use of the live rodent organism according to claim 2 , wherein the genes or gene sections genetically engineered are single or multistage immunoeffectors are liver-stage antigens such as circumsporozoite protein (CS) claim 2 , liver stage antigen 1 (LSA-1) claim 2 , thrombospondin-related adhesion protein (TRAP) claim 2 , and liver stage antigen 3 (LSA-3) or blood-stage antigens such as erythrocyte-binding antigen-175 (EBA-175) claim 2 , apical membrane antigen-1 (AMA-I) claim 2 , merozoite surface protein 1 (MSP-1) claim 2 , Duffy-binding protein (DBP) claim 2 , and reticulocyte-binding proteins (RBPs) claim 2 , or gametocyte-specific antigens such as p48/45 claim 2 , or other immunogenic antigens.5PlasmodiumPlasmodiumPlasmodiumP. falciparum, P. vivax, P. malariae, P. ovaleP. knowlesi.. The use of the live rodent organism according to claim 1 , wherein the human malaria is caused by any of the human parasite from the protozoan genus including and6Plasmodium. The use of the live rodent organism described in claim 1 , for the manufacture of an admixture with a pharmaceutically acceptable carrier.7Plasmodium. The use of the live rodent organism according to claim 6 , for the manufacture of a vaccine against human malaria. This ...

PD-1 Peptide Inhibitors

This disclosure provides peptides which have a strong affinity for the checkpoint receptor “programmed death 1” (PD-1). These peptides block the interaction of PD-1 with its ligand PD-L1 and can therefore be used for various therapeutic purposes, such as inhibiting the progression of a hyperproliferative disorder, including cancer, treating infectious diseases, enhancing a response to vaccination, and treating sepsis. 1. A pharmaceutical composition , comprising: (i) a peptide consisting of the amino acid sequence SEQ ID NO:1;', '(ii) a peptide consisting of the amino acid sequence SEQ ID NO:2;', '(iii) a peptide consisting of the amino acid sequence SEQ ID NO:3; and', '(iv) a peptide consisting of the amino acid sequence SEQ ID NO:4; and, '(a) up to four peptides selected from the group consisting of(b) a pharmaceutically acceptable vehicle.2. The pharmaceutical composition of claim 1 , which comprises only one of the four peptides.3. The pharmaceutical composition of claim 1 , which comprises only two of the four peptides claim 1 , wherein the two peptides are selected from the group consisting of:(a) the peptide consisting of the amino acid sequence SEQ ID NO:1 and the peptide consisting of the amino acid sequence SEQ ID NO:2;(b) the peptide consisting of the amino acid sequence SEQ ID NO:1 and the peptide consisting of the amino acid sequence SEQ ID NO:3;(c) the peptide consisting of the amino acid sequence SEQ ID NO:1 and the peptide consisting of the amino acid sequence SEQ ID NO:4;(d) the peptide consisting of the amino acid sequence SEQ ID NO:2 and the peptide consisting of the amino acid sequence SEQ ID NO:3;(e) the peptide consisting of the amino acid sequence SEQ ID NO:2 and the peptide consisting of the amino acid sequence SEQ ID NO:4; and(f) the peptide consisting of the amino acid sequence SEQ ID NO:3 and the peptide consisting of the amino acid sequence SEQ ID NO:4.4. The pharmaceutical composition of claim 1 , which comprises only three of the four ...

Malaria Vaccines Based on Pre-Erythrocytic Antigens From P. Falciparum

The present invention relates to polypeptides or fragments thereof for use as malaria vaccines. It also relates to nucleic acid molecules coding for the polypeptides of the invention. It further relates to compositions comprising such polypeptides or fragments thereof or the nucleic acid molecules, in particular combinations of such polypeptides or fragments thereof, and the use of such compositions as malaria vaccines. 2. The multicomponent malaria vaccine claim 1 , according to claim 1 , wherein the vaccine comprises a mixture of polypeptides comprising the sequences of SEQ ID NOs: 26 to 28 and SEQ ID NOs: 31 to 33.4. The multicomponent malaria vaccine claim 1 , according to claim 1 , wherein the vaccine further comprises polypeptides selected from the following polypeptides:a mixture of SEQ ID NOs: 29 and 30;a mixture of SEQ ID NOs: 34 and 35;SEQ ID NO: 36; anda mixture of SEQ ID NOs: 37 to 40.5. The multicomponent malaria vaccine claim 1 , according to claim 1 , wherein the polypeptides comprise one or more labels claim 1 , N- and/or C-terminal modifications claim 1 , or a drug.6. The multicomponent malaria vaccine claim 1 , according to claim 1 , wherein the adjuvant triggers a CD8 T cell response.7. The multicomponent malaria vaccine according to claim 1 , wherein the vaccine comprises a mixture of polypeptides comprising the sequences of SEQ ID NOs: 26 to 28.8. The multicomponent malaria vaccine according to claim 1 , wherein the vaccine comprises a mixture of polypeptides comprising the sequences of SEQ ID NOs: 31 to 33.9. A method for vaccinating against malaria claim 1 , wherein said method comprises administering claim 1 , to a subject in need of such vaccination claim 1 , the multicomponent malaria vaccine according to . This application is a Continuation Application of co-pending application Ser. No. 13/988,339, filed Aug. 7, 2013; which is a National Stage Application of International Application Number PCT/EP2011/006110, filed Dec. 6, 2011; which ...

Plasmodium falciparum antigens

The invention relates to antigens, associated with sterile immunity, and methods of their use, in an immunogenic formulation to confer an immune response against . The inventive antigens were identified by their association with sterile immunity against malaria. 1Plasmodium falciparum. An immunogenic composition comprising the isolated protein expressed by sporozoites encoded by the loci PFD0485.2. The immunogenic composition of claim 1 , wherein the isolated protein has the amino acid sequence of SEQ ID No. 8 or immunogenic fragments or derivatives claim 1 , thereof.3Plasmodium falciparum. The immunogenic composition of claim 1 , wherein the composition also comprises isolated proteins expressed by sporozoites encoded by one or more of the loci selected from the group consisting of PF10925w claim 1 , PFB0285c claim 1 , PF140051 claim 1 , PFL1620w claim 1 , PF100211 claim 1 , PFB0150c claim 1 , PF110344 claim 1 , PFE0060w claim 1 , PF080034 claim 1 , PF080054 claim 1 , PF2140c claim 1 , PFC0210c claim 1 , PFE1085w claim 1 , PF110404 claim 1 , PF130201 claim 1 , PFL2505c claim 1 , PF130222 claim 1 , and MAL13P1.22.4. The immunogenic composition of claim 2 , wherein the isolated protein encoded by the loci PFD0485 with the amino acid sequence of SEQ ID No. 8 claim 2 , or immunogenic fragments or derivatives claim 2 , thereof claim 2 , is expressed from a nucleotide sequence inserted into a suitable expression vector capable of protein expression in a mammal claim 2 , wherein the nucleotide sequence comprises the nucleotide sequence of SEQ ID No. 7 claim 2 , or nucleotide sequences encoding immunogenic fragments or deriviatives of the amino acid sequence of SEQ ID No. 8.5. The immunogenic composition of claim 3 , wherein the isolated proteins have the amino acid sequences selected from the group consisting of claim 3 , with the amino acid sequences of SEQ ID No. 2 claim 3 , SEQ ID No. 4 claim 3 , SEQ ID No. 6 claim 3 , SEQ ID No. 10 claim 3 , SEQ ID No. 12 claim 3 , ...

ATTENUATED PLASMODIUM WITH DEACTIVATED HMGB2 GENE, AS VACCINE

The present invention relates to novel compositions and methods for immunizing a host against malaria using a parasite genetically attenuated via the inactivation of the function of the hmgb2 gene. 1Plasmodium. A method of preventing malaria or cerebral malaria in a mammal , comprising administering a live parasite belonging to the genus in which the function of the hmgb2 gene is inactivated.2of Plasmodium berghei, Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariaeknowlesi.. The method of claim 1 , wherein the strain of the parasite is selected from the group consisting and Plasmodium3Plasmodium falciparum, Plasmodium vivax, Plasmodium ovalePlasmodium malariae.. The method of claim 2 , wherein the strain of the parasite is selected from the group consisting of and4Plasmodium falciparum.. The method of claim 3 , wherein the strain of the parasite is5. The method of claim 4 , wherein the parasite in its wild-type form does not cause cerebral malaria.6Plasmodium berghei. The method of claim 1 , wherein the strain of the parasite is NK65.7Plasmodium falciparum. The method of claim 1 , wherein the strain of the parasite is a strain that is non-cytoadherent or that has a reduced cytoadherence capacity.8Plasmodium falciparum. The method of claim 7 , wherein the strain of the parasite is a strain that has a reduced cytoadherence capacity.9. The method of claim 1 , wherein the parasite is in the form of non-intra-erythrocytic merozoites.10. The method of claim 1 , wherein the parasite is in an intra-erythrocytic form.11. The method of claim 10 , wherein the parasite is in the form of intra-erythrocytic trophozoites claim 10 , merozoites or schizonts.12. The method of claim 11 , wherein the parasite is in the form of intra-erythrocytic merozoites or schizonts.13. The method of claim 1 , wherein the parasite is in the form of sporozoites.14. The method of claim 1 , wherein the function of the hmgb2 gene is inactivated by total or partial deletion of ...

ISG15 AND ITS USE AS AN ADJUVANT

Disclosed herein is a vaccine comprising an antigen and ISG15. Also disclosed herein is a method for increasing an immune response in a subject in need thereof. Further disclosed herein is a method for treating a subject in need thereof. The methods may comprise administering the vaccine to the subject. 1. A vaccine comprising an antigen and ISG15.2. The vaccine of claim 1 , wherein ISG15 is encoded by a nucleotide sequence selected from the group consisting of: a nucleotide sequence having at least about 95% identity to a nucleotide sequence as set forth in SEQ ID NO:1 claim 1 , a nucleotide sequence as set forth in SEQ ID NO:1 claim 1 , a nucleotide sequence having at least about 95% identity to a nucleotide sequence as set forth in SEQ ID NO:3 claim 1 , a nucleotide sequence as set forth in SEQ ID NO:3 claim 1 , a nucleotide sequence having at least about 95% identity to a nucleotide sequence as set forth in SEQ ID NO:5 claim 1 , a nucleotide sequence as set forth in SEQ ID NO:5 claim 1 , a nucleotide sequence having at least about 95% identity to a nucleotide sequence as set forth in SEQ ID NO:7 claim 1 , a nucleotide sequence as set forth in SEQ ID NO:7 claim 1 , a nucleotide sequence having at least about 95% identity to a nucleotide sequence as set forth in SEQ ID NO:9 claim 1 , and a nucleotide sequence as set forth in SEQ ID NO:9.3. The vaccine of claim 2 , wherein ISG15 is encoded by the nucleotide sequence as set forth in SEQ ID NO:1.4. The vaccine of claim 2 , wherein ISG15 is encoded by the nucleotide sequence as set forth in SEQ ID NO:3.5. The vaccine of claim 2 , wherein ISG15 is encoded by the nucleotide sequence as set forth in SEQ ID NO:5.6. The vaccine of claim 2 , wherein ISG15 is encoded by the nucleotide sequence as set forth in SEQ ID NO:7.7. The vaccine of claim 2 , wherein ISG15 is encoded by the nucleotide sequence as set forth in SEQ ID NO:9.8. The vaccine of claim 1 , wherein the antigen is encoded by a first nucleic acid and ISG15 is ...

Plasmodium falciparum antigens

The invention relates to antigens, associated with sterile immunity, and methods of their use, in an immunogenic formulation to confer an immune response against . The inventive antigens were identified by their association with sterile immunity against malaria. 1Plasmodium falciparum. An immunogenic composition comprising the isolated protein expressed by sporozoites encoded by the loci PFD0485.2. The immunogenic composition of claim 1 , wherein the isolated protein has the amino acid sequence of SEQ ID No. 8 or immunogenic fragments or derivatives claim 1 , thereof.3Plasmodium falciparum. The immunogenic composition of claim 1 , wherein the composition also comprises isolated proteins expressed by sporozoites encoded by one or more of the loci selected from the group consisting of PF10925w claim 1 , PFB0285c claim 1 , PF140051 claim 1 , PFL1620w claim 1 , PF100211 claim 1 , PFB0150c claim 1 , PF110344 claim 1 , PFE0060w claim 1 , PF080034 claim 1 , PF080054 claim 1 , PF2140c claim 1 , PFC0210c claim 1 , PFE1085w claim 1 , PF110404 claim 1 , PF130201 claim 1 , PFL2505c claim 1 , PF130222 claim 1 , and MAL13P1.22.4. The immunogenic composition of claim 2 , wherein the isolated protein encoded by the loci PFD0485 with the amino acid sequence of SEQ ID No. 8 claim 2 , or immunogenic fragments or derivatives claim 2 , thereof claim 2 , is expressed from a nucleotide sequence inserted into a suitable expression vector capable of protein expression in a mammal claim 2 , wherein the nucleotide sequence comprises the nucleotide sequence of SEQ ID No. 7 claim 2 , or nucleotide sequences encoding immunogenic fragments or deriviatives of the amino acid sequence of SEQ ID No. 8.5. The immunogenic composition of claim 3 , wherein the isolated proteins have the amino acid sequences selected from the group consisting of claim 3 , with the amino acid sequences of SEQ ID No. 2 claim 3 , SEQ ID No. 4 claim 3 , SEQ ID No. 6 claim 3 , SEQ ID No. 10 claim 3 , SEQ ID No. 12 claim 3 , ...

NOVEL VACCINES AGAINST APICOMPLEXAN PATHOGENS

The technology provided herein generally relates to novel fusion proteins suitable as human and/or animal vaccines against parasites or pathogens of the phylum Apicomplexa. In particular, the present disclosure relates to novel fusion proteins as a basis for vaccines against parasites, including and . Nucleic acid molecules encoding said fusion proteins, vectors, host cells containing the nucleic acids and methods for preparation and producing such fusion proteins; antibodies induced or generated by the use of said fusion proteins or said nucleic acid molecules encoding said fusion proteins and the use of such antibodies or recombinant derivatives for passive immunotherapy; methods for producing such fusion proteins; compositions and methods for using such fusion proteins for the prevention and treatment of malaria are also encompassed by the present disclosure. 1. A recombinant fusion protein suitable as a human and/or animal vaccine against a parasite of the phylum Apicomplexa comprising a plurality of isolated heat stable fragments derived from at least two different Apicomplexa surface proteins presented on the surface of the parasite in at least two different life cycle main stages of the parasite , wherein each fragment contains at least one folded domain.2. The recombinant fusion protein according to claim 1 , wherein the fusion protein comprises at least four different isolated heat stable fragments.3. The recombinant fusion protein according to claim 1 , wherein the folded domain is an EGF-like domain or a TSR domain.4. The recombinant fusion protein according to claim 1 , wherein the recombinant fusion protein comprises further at least one non-heat stable isolated fragment derived from an Apicomplexa surface protein claim 1 , wherein the entire fusion protein is heat stable.5. The recombinant fusion protein according to claim 1 , wherein the fusion protein has a cysteine content of at least 5% claim 1 , in particular of at least 7.5% claim 1 , more ...

ANTI-MALARIA COMPOSITIONS AND METHODS

Multilayer films comprise polypeptide epitopes from , specifically a circumsporozoite CIS43 epitope and one or more of circumsporozoite T1, B or T* epitope. The multilayer films are capable of eliciting an immune response in a host upon administration to the host. The multilayer films can include at least one designed peptide that includes one or more polypeptide epitopes from a protozoan. 1. A composition comprisinga multilayer film comprising a plurality of oppositely charged polyelectrolyte layers,{'i': 'Plasmodium falciparum', 'sup': 'M', '#text': 'wherein one of the polyelectrolyte layers in the multilayer film comprises an antigenic polyelectrolyte, wherein the antigenic polyelectrolyte comprises a circumsporozoite CIS43 epitope of SEQ ID NO: 6 and one or more of T1, B, T* and T*epitopes covalently linked to the antigenic polyelectrolyte;'}wherein the polyelectrolytes in the multilayer film comprise a polycationic material or a polyanionic material having a molecular weight of greater than 1,000 daltons and at least 5 charges per molecule.2Plasmodium falciparum. The composition of claim 1 , wherein the antigenic polyelectrolyte comprises two of the circumsporozoite T1 claim 1 , B claim 1 , and T*; or T1 claim 1 , B claim 1 , and T*epitopes.3Plasmodium falciparum. The composition of claim 1 , wherein the antigenic polyelectrolyte comprises all three of the circumsporozoite T1 claim 1 , B claim 1 , T* and T*epitopes.4. The composition of claim 1 , wherein the first antigenic polyelectrolyte is a polypeptide.5. The composition of claim 1 , wherein the multilayer film further comprises a TLR ligand.6. The composition of claim 1 , wherein the multilayer film is deposited on a core particle.7. The composition of claim 6 , wherein the antigenic polyelectrolyte is in the outermost layer of the multilayer film.8. A composition comprisinga multilayer film comprising a plurality of oppositely charged polyelectrolyte layers,{'i': 'Plasmodium falciparum', '#text': 'wherein ...

Immunoproteasome Inhibitor

Methods and pharmaceutical compositions for treating malaria and immune related disorders are provided. The pharmaceutical compositions include an effective amount a carmaphycin B analog that inhibits immunoproteasome activity in a subject. 1. A method for treating a disease comprising:administering to a subject in need thereof an effective amount of a composition comprising a carmaphycin B analog, wherein the carmaphycin B analog has methionine sulfone replaced with norleucine in position P2, and wherein the carmaphycin B analog has decreased cytotoxicity and increased selectivity for inhibiting immunoproteasome activity over constitutive proteasome activity as compared to carmaphycin B.2. The method of claim 1 , wherein the subject is a human.3. The method of claim 1 , wherein the disease is malaria.4. The method of claim 1 , wherein the disease is an immune related disorder.5. The method of claim 1 , wherein the disease is cancer.6. The method of claim 1 , wherein the disease is rheumatoid arthritis.7. The method of claim 1 , wherein the carmaphycin B analog has L-Val replaced with D-Val or D-Trp in position P3.8. The method of claim 1 , wherein the carmaphycin B analog is Analog 18: (S)-2-((R)-2-hexanamido-3-methylbutanamido)-N—((S)-4-methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-yl)hexanamide.9. The method of claim 1 , wherein the carmaphycin B analog is Analog 19: (S)-2-((R)-2-hexanamido-3-(1H-indol-3-yl)propanamido)-N—((S)-4-methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-yl)hexanamide.10. The method of claim 1 , wherein the carmaphycin B analog is Analog 1: (S)-2-((S)-2-hexanamido-3-methylbutanamido)-N—((S)-4-methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-yl)hexanamide.11. The method of claim 1 , wherein the carmaphycin B analog specifically inhibits a β5 subunit of the immunoproteasome.12. A pharmaceutical composition for treating a disease or disorder associated with immunoproteasome activity comprising:a carmaphycin B analog, wherein the carmaphycin ...

PLASMODIAL SURFACE ANION CHANNEL INHIBITORS FOR THE TREATMENT OR PREVENTION OF MALARIA

The invention provides methods of treating or preventing malaria comprising administering to an animal an effective amount of a compound of formula I: 141-. (canceled)42. A pharmaceutical composition comprising: {'br': None, 'sup': 1', '2, 'Q-Y—R—R\u2003\u2003(I),'}, 'i) a compound of formula (I)wherein:Q is selected from the group consisting of a dioxo heterocyclyl ring fused to an aryl group, a heterocyclic amido group linked to a heterocyclic group, alkyl, a heterocyclic group fused to a heterocyclic amido group, arylamino carbonyl, amino, heterocyclic amido, and heterocyclic amino group, each of which, other than amino, is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxy, mercapto, alkoxy, alkylthio, nitro, cyano, amino, alkyl, aryl, hydroxyalkyl, haloalkyl, cyanoalkyl, aminoalkyl, alkylamino, dialkylamino, carboxy, carboxyalkyl, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, ureido, and formyl;{'sub': '2', 'Y is a bond, S, SO, or amido;'}{'sup': '1', 'Ris divalent group selected from the group consisting of a heterocyclic ring having at least one nitrogen atom, piperidinyl, piperazinyl, aryl, a heterocyclic ring having at least one nitrogen atom linked to an alkylamino group, benzo fused heterocyclyl, heterocyclyl fused to an iminotetrahydropyrimidino group, and heterocyclyl fused to a heterocyclic amido group, each of which is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxy, mercapto, alkoxy, alkylthio, nitro, cyano, amino, alkyl, hydroxyalkyl, haloalkyl, cyanoalkyl, aminoalkyl, alkylamino, dialkylamino, carboxy, carboxyalkyl, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, ureido, and formyl;'}{'sup': '2', 'Ris selected from the group consisting of arylalkenyl, heterocyclyl carbonylamino, heterocyclyl alkylamino, tetrahydroquinolinyl alkenyl, tetrahydroisoquinolinyl alkyl, indolylalkenyl, dihydroindolylalkenyl, aryloxyalkyl, arylalkyl, diazolyl, and ...

ENHANCEMENT OF PATHOGEN IMMUNOGENICITY

The present invention relates to a vaccine composition for use in in vivo administration, comprising a (attenuated) pathogen or commensal modified to be a pre-targeting vector, the pre-targeting vector comprising one or more pendent reactive moieties able to form a high affinity interaction with a complementary moiety residing on an immunogenic conjugate component. 1. A two component vaccine composition for use in in vivo administration , comprising a (preferably attenuated) pathogen or commensal modified as a pre-targeting vector , the pre-targeting vector comprising one or more pendent reactive moieties able to form a high affinity interaction with a complementary conjugate moiety residing on an immunogenic secondary component.2. A The composition of claim 1 , wherein the high affinity interaction comprises a supramolecular vector-conjugate interaction in an inclusion affinity complex.3. The composition of claim 1 , wherein a primary moiety on the vector surface is selected from the group consisting of streptavidin claim 1 , cyclodextrin claim 1 , antibodies claim 1 , antibody fragments claim 1 , ligands and aptamers claim 1 , and wherein the conjugate moiety is a moiety complementary to the respective vector moiety.4. The composition of claim 3 , wherein the vector moiety comprises adamantane groups claim 3 , and wherein the conjugate moiety includes cyclodextrin groups.5. The composition of claim 1 , wherein the high affinity interaction comprises formation of one or more covalent bonds.6. The composition of claim 5 , wherein the pathogen or commensal is functionalised to form a covalent click connection with a conjugate moiety claim 5 , preferably using copper-free click chemistry.7. The composition of claim 5 , wherein the vector moiety comprises one or more azide groups claim 5 , and wherein the conjugate moiety linked to the pathogen comprises one or more reactive alkyne groups claim 5 , preferably wherein both groups are suited for copper-free click ...

AN IMPROVED ADENOVIRUS BASED MALARIA VACCINE ENCODING AND DISPLAYING A MALARIA ANTIGEN

The present invention relates to novel vaccines against malaria infections, based on recombinant adenovirus vectors. Described are capsid modified replication deficient adenovirus particle encoding and displaying circumsporozoite (CS) protein NANP-repeats (CS) from a malaria-causing parasite, preferably via a minor capsid protein IX and encoding a heterologous protein as a transgene. In a particular embodiment, said replication incompetent vectors of rare serotypes such as human adenovirus 35 (HAdV35) and human adenovirus 26 (HAdV26) comprise nucleic acid encoding the CS protein, as a transgene, from a malaria-causing parasite and encoding and displaying the NANP-repeat from a malaria-causing parasite (1) directly fused to the protein IX, (2) fused to protein IX via a flexible linker or (3) an alpha-helical viral origin spacer SP1 to ensure both humoral and cellular responses against the selected antigens. 1Plasmodium falciparum,. A recombinant adenoviral vector comprising a nucleic acid encoding a capsid comprising a fusion protein consisting of a protein IX and a fragment of a circumsporozoite (CS) protein of wherein said fragment comprises the amino acid sequence of SEQ ID NO:1.2. The recombinant adenoviral vector according to claim 1 , wherein said fusion protein comprises a linker located in between the pIX protein and the CS protein fragment.3. The recombinant adenoviral vector according to claim 2 , wherein the linker comprises an amino acid sequence having 2 to 15 consecutive flexible residues of glycine and/or serine.4. The recombinant adenoviral vector according to claim 1 , wherein said fusion protein comprises a spacer claim 1 , located in between the pIX protein and the CS protein fragment.5. The recombinant adenoviral vector according to claim 4 , wherein said spacer comprises the amino acid sequence of SEQ ID NO:2.6. The recombinant adenoviral vector according to claim 4 , wherein said spacer comprises the amino acid sequence of SEQ ID NO:3.7. The ...

IMMUNOGENIC COMPOSITIONS AND EXPRESSION SYSTEMS

Immunogenic compositions and vaccines against Plasmodial infection comprising an Rh polypeptide or a fragment or variant thereof are disclosed. Also disclosed are Rh5 polypeptides or fragments or variants thereof capable of binding CD147 and conferring protection against infection and/or disease caused by multiple Plasmodial strains or Plasmodial species, inhibitors of the interaction between Rh5 and CD147 and methods for producing polypeptides in a mammalian expression system. 127-. (canceled)28PlasmodiumPlasmodium.. A method of preventing and/or treating infection and/or disease comprising administering to a subject in need thereof an immunogenic composition or vaccine comprising an Rh5 polypeptide , fragment , or variant thereof from29. The method of claim 28 , wherein the Rh5 polypeptide or fragment or variant thereof has been shown to bind to CD147.30. The method of claim 29 , wherein the Rh5 polypeptide or fragment or variant thereof has been shown to bind to CD147 with a kD of at least 1 μM.31. The method of claim 28 , wherein the immunogenic composition or vaccine comprises additional antigens claim 28 , such as Plasmodial antigens.32PlasmodiumPlasmodium. A method of conferring cross-protection to multiple strains comprising administering to a subject in need thereof an immunogenic composition or vaccine comprising an Rh5 polypeptide claim 28 , fragment claim 28 , or variant thereof from which has been shown to bind CD147.33. The method of claim 32 , wherein the Rh5 polypeptide or fragment or variant thereof has been shown to bind to CD147.34. The method of claim 33 , wherein the Rh5 polypeptide or fragment or variant thereof has been shown to bind to CD147 with a kD of at least 1 μM.35. The method of claim 32 , wherein the immunogenic composition or vaccine comprises additional antigens claim 32 , such as Plasmodial antigens.36PlasmodiumPlasmodium. Plasmodium. A method of inducing immunity against multiple strains comprising administering to a subject in ...

PRODUCTION OF A CYSTEINE RICH PROTEIN

The present invention relates to a method for the production of correctly folded Pfs48/45. This is achieved in the when Pfs48/45 or fractions thereof are fused genetically to a glutamate rich protein, e.g. GLURP from 1. A method of producing a cysteine-rich protein where the cysteine-rich protein is fused to a glutamate-rich protein in a lactic acid bacterial system , where the formation of monomeric fusion protein is enhanced by controlling the redox potential in the lactic acid bacterial production medium by adding reduced forms of L-cysteine or DTT or glutathione or TCEP or cysteamine or any other small sulfhydryl containing compound.2. The method according to claim 1 , where the glutamate-rich protein is GLURP or part of GLURP.3Lactococcus lactis. The method according to where the lactic acid bacterium is45-. (canceled)6. The method according to where L-cysteine is added to the medium to a concentration of 5-20 mM to enhance the formation of monomeric fusion protein.7Plasmodium falciparum.. The method according to where the cysteine-rich protein originates from8. The method according to where the cysteine-rich protein is Pfs48/45 claim 7 , Pfs25 claim 7 , Pfs230 claim 7 , Pfs47 claim 7 , EBA175 claim 7 , a member of the PfEMP1 claim 7 , RIFIN or STEVOR protein families or a fragment or a homologue hereof.9. The method according to where the correct folding of the cysteine rich protein is enhanced by addition of reduced and oxidized forms of L-cysteine or DTT or glutathione or TCEP or cysteamine or any other small sulfhydryl containing compound capable of reducing or oxidixing cystines or cysteines in proteins to the buffer during the down-stream processing.10. The method according to where 1-10 mM of the reduced form and 0.1-5 mM of the oxidized form of the sulfhydryl containing compound is added.11. A fusion protein produced according to .12. A fusion protein comprising SEQ ID NO: 5 claim 1 , SEQ ID NO: 25 claim 1 , or a homologue of SEQ ID NO: 5 or SEQ ID NO: ...

MALARIAL ANTIGENS DERIVED FROM SUBTILISIN-LIKE PROTEASE 2 AND VACCINES AND METHODS OF USE

The present invention provides immunogenic compositions comprising one or more subtilisin-like protease 2 antigens, functional fragments or homologs thereof, from various species, methods, vectors comprising the antigens, and methods of use for the treatment of malaria and related disease. 1Plasmodium. An immunogenic composition comprising one or more subtilisin-like protease 2 antigens from and a pharmaceutically acceptable carrier.2P. berghei, P. falciparum, P. vivax, P. knowlesi,P. yoelli.. The immunogenic composition of claim 1 , wherein the subtilisin-like protease 2 antigens are selected from and3. The immunogenic composition of claim 1 , wherein the subtilisin-like protease antigen has an amino acid sequence selected from the group consisting of SEQ ID NOS: 1-12.4. The immunogenic composition of claim 3 , further comprising an adjuvant.5. The immunogenic composition claim 3 , further comprising at least one additional therapeutic agent.6Plasmodium.. A vector comprising one or more subtilisin-like protease 2 antigens from7P. berghei, P. falciparum, P. vivax, P. knowlesi,P. yoelli.. The vector of claim 6 , wherein the subtilisin-like protease 2 antigens are selected from and8. The vector of claim 6 , wherein the subtilisin-like protease has an amino acid sequence selected from the group consisting of SEQ ID NOS: 1-12.9. The vector of claim 7 , wherein the subtilisin-like protease 2 antigens are codon harmonized.10. A cell expressing the vector of .11Plasmodium. A method for blocking transmission of a infection in a subject comprising administering to the subject an effective amount of the immunogenic composition of .12P. berghei, P. falciparum, P. vivax, P. knowlesi,P. yoelli.. The method of claim 11 , wherein the subtilisin-like protease 2 antigens are selected from and13. The method of claim 11 , wherein the subtilisin-like protease antigen has an amino acid sequence selected from the group consisting of SEQ ID NOS: 1-12.14. The method of claim 11 , further ...

Methods and Compositions for Preventing a Condition

Provided herein are methods, compositions, and kits for preventing, inhibiting, reducing the severity of, or treating a disease or condition. A pharmaceutical composition provided herein can comprise a nucleic acid sequence encoding an antigen fused to an immune cell product, e.g., MIP-3α, and an adjuvant. The antigen can be from a bacteria, virus, fungus, parasite, or cancer. The antigen can be an Alzheimer's disease antigen. 1. A pharmaceutical composition comprising:a. a nucleic acid sequence encoding an antigen or a fragment thereof fused to macrophage inflammatory protein 3 alpha or a fragment thereof; andb. an adjuvant.2. The pharmaceutical composition of claim 1 , wherein the antigen or a fragment thereof is a cancer antigen.3. (canceled)4. (canceled)5. The pharmaceutical composition of claim 1 , wherein the antigen or a fragment thereof is from a parasite.6. (canceled)7. (canceled)8. (canceled)9. The pharmaceutical composition of claim 1 , wherein the adjuvant is a liposome.10. (canceled)11. The pharmaceutical composition of claim 1 , further comprising a regulatory T-cell inhibitor.12. The pharmaceutical composition of claim 11 , wherein the regulatory T-cell inhibitor is an siRNA.13. The pharmaceutical composition of claim 1 , wherein the nucleic acid sequence is a plasmid.14. The pharmaceutical composition of claim 1 , wherein the nucleic acid sequence encodes human macrophage inflammatory protein 3 alpha or a fragment thereof.15. A nucleic acid sequence encoding a parasite antigen fused to macrophage inflammatory protein 3 alpha.16Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariaPlasmodium yoelii.. The nucleic acid sequence of wherein the parasite is claim 15 , or17. The nucleic acid sequence of wherein the antigen is a circumsporozoite protein or fragment thereof.18Plasmodium falciparum.. The nucleic acid sequence of wherein the circumsporozoite protein or fragment thereof is from19. The nucleic acid sequence of claim 17 , ...

PLASMODIUM SPOROZOITE NPDP PEPTIDES AS VACCINE AND TARGET NOVEL MALARIA VACCINES AND ANTIBODIES BINDING TO

The present invention provides a fragment of plasmodium circumsporozoite protein according to SEQ ID NO: 1, for example for use in a malaria vaccine. The present invention also provides nucleic acids encoding a fragment of plasmodium circumsporozoite protein according to SEQ ID NO: 1, compositions comprising a fragment of plasmodium circumsporozoite protein according to SEQ ID NO: 1 and antibodies binding to a fragment of plasmodium circumsporozoite protein according to SEQ ID NO: 1. The antibodies according to the present invention bind specifically to sporozoites and may be used in the treatment and/or prevention of malaria. 1. A peptide comprising or consisting of the amino acid sequence according to SEQ ID NO: 1.23.-. (canceled)4. The peptide according to claim 1 , wherein the peptide comprises or consists of an amino acid sequence according to SEQ ID NO: 23 or shares at least 72% claim 1 , at least 77% claim 1 , at least 83% claim 1 , at least 88% claim 1 , or at least 94% sequence identity with SEQ ID NO. 23.511.-. (canceled)12. A method of preventing and/or treating malaria claim 1 , the method comprising administering to a subject in need thereof a composition comprising the peptide according to .13. A method of eliciting an immune response in a subject claim 1 , the method comprising administering to the subject a composition comprising the peptide according to .1434.-. (canceled)35. An antibody claim 1 , or an antigen-binding fragment thereof claim 1 , specifically binding to a peptide according to .3638.-. (canceled)39. The antibody claim 35 , or the antigen-binding fragment thereof claim 35 , according to claim 35 , wherein the antibody claim 35 , or antigen binding fragment thereof claim 35 , comprises an Fc moiety.40. The antibody claim 35 , or the antigen-binding fragment thereof claim 35 , according to claim 35 , wherein the variable region of the heavy chain of the antibody claim 35 , or of the antigen-binding fragment thereof claim 35 , is encoded ...

VACCINES

The present invention relates to particles, particularly virus-like particles (VLPs), comprising fusion polypeptides comprising selected repeat units derived from the repeating regions of Type I and Type II circumsporozoite proteins (CSP) of (Pv), together with an amino acid sequence derived from the C-terminal PvCSP sequence. In some embodiments, the fusion polypeptide additionally comprises an amino acid sequence derived from the N-terminal PvCSP sequence and/or a surface antigen polypeptide derived from Hepatitis B virus (HBV-S). The invention also relates to nucleotide sequences coding for such fusion polypeptides, vectors and plasmids comprising such nucleotide sequences, and host cells comprising such vectors and plasmids. The invention additionally relates to compositions, particularly vaccine compositions, comprising the fusion polypeptides or VLPs for use as vaccines for the prevention of malaria. 134.-. (canceled)35. A fusion polypeptide or a particle comprising the fusion polypeptide , wherein the fusion polypeptide comprises:{'i': 'Plasmodium vivax;', '(i) at least 6 repeat units derived from the repeating region of a Type I circumsporozoite protein (CSP) of'}{'i': 'Plasmodium vivax', '(ii) at least 6 repeat units derived from the repeating region of a Type II circumsporozoite protein (CSP) of ; and'}{'i': 'Plasmodium vivax', '(iii) an amino acid sequence derived from the C-terminal fragment of CSP of ; and optionally'}(iv) an amino acid sequence derived from the Hepatitis B virus surface antigen.36. The fusion polypeptide or particle as claimed in claim 35 , wherein the fusion polypeptide comprises:{'i': 'Plasmodium vivax', '(i) 8-12 repeat units derived from the repeating region of a Type I circumsporozoite protein (CSP) of ; and/or'}{'i': 'Plasmodium vivax.', '(ii) 8-12 repeat units derived from the repeating region of a Type II circumsporozoite protein (CSP) of'}37. The fusion polypeptide or particle as claimed in claim 35 , wherein the fusion ...

Blood Stage Malaria Vaccine

An immunogenic composition for use as a blood-stage malaria vaccine, a method of producing the immunogenic composition and a method of treatment of malaria are provided. The immunogenic composition includes isolated or purified merozoites, or red blood cells infected with merozoites, treated with centanamycin or tafuramycin A. The immunogenic composition does not include an adjuvant. A single dose of the immunogenic composition is sufficient to protect an animal against subsequent malaria infection by the same isolate, strain or species of used in the immunogenic composition, or by one or more heterologous isolates, strains or species of 1. A method of producing an immunogenic composition including the step of treating blood-stage malaria parasites or red blood cells infected with said blood-stage malaria parasites with centanamycin , tafuramycin A or an analog or derivative thereof , to thereby produce said immunogenic composition.2. The method of claim 1 , wherein the method excludes the step of including an adjuvant.3. The method of claim 1 , wherein isolated or purified blood-stage parasites are treated with centanamycin claim 1 , tafuramycin A or an analog or derivative thereof.4. The method of claim 3 , wherein red blood cells are subsequently infected with the treated blood-stage parasites to produce parasitized red blood cells (pRBC).5. The method of claim 1 , wherein red blood cells infected with blood-stage parasites (pRBC) are treated with centanamycin claim 1 , tafuramycin A or an analog or derivative thereof.6. The method of claim 1 , which comprises a low dose of blood-stage malaria parasites or red blood cells infected with the blood-stage malaria parasites (parasitized red blood cells; pRBC).7. The method of claim 6 , wherein the low dose is less than 10blood-stage malaria parasites or treated pRBC.8. The method of claim 7 , wherein the low dose is selected from the group consisting of: less than 10blood-stage malaria parasites or pRBC claim 7 , less ...

Uses of parasite macrophage migration inhibitory factors

This invention relates to compositions (e.g. vaccine compositions) which can be used to provide a subject with protective immunity against a parasite infection. The compositions comprise: (i) an immunologically effective amount of a nucleic acid (e.g. a nucleic acid-based vaccine) comprising a sequence which encodes a parasite macrophage migration inhibitory factor (MIF) antigen; (ii) a parasite MIF antigen; or (iii) an antibody which specifically binds to a parasite MIF antigen. The compositions may be used to treat infections and diseases caused by parasitic protozoans, such as a Plasmodium parasite, or parasitic helminths.

MULTI-COMPONENT-MULTISTAGE MALARIA VACCINES

The present disclosure relates to novel malaria vaccines composed of different recombinant proteins, in particular recombinant fusion proteins comprising several different antigens from the pre-erythrocytic the blood, and the sexual parasite stages. The proteins and/or fusion proteins will be used in a mixture vaccine formulation to elicit protective immune responses in humans. Nucleic acid molecules encoding said recombinant proteins, vectors, host cells containing the nucleic acids and methods for preparation and producing such proteins; Antibodies induced or generated by the use of said malaria vaccines or said nucleic acid molecules encoding said proteins and/or fusion proteins and the use of such antibodies or recombinant derivatives for passive immunotherapy. 1Plasmodium falciparumPlasmodium falciparum. A mixture of recombinant proteins suitable as a human vaccine against the parasite comprising antigens from surface proteins of the pre-erythrocytic , the blood- , and the sexual-stage of the parasite life cycle , whereina) the pre-erythrocytic antigens comprise at least the antigens PfCelTOS, PfCSP and PfTRAP, or domains, variants or fragments thereof, andb) the blood stage antigen(s) comprise at least one or more variants of Apical membrane antigen 1 (PfAMA1), or fragments thereof; andc) the sexual stage antigen(s) comprise the ookinete antigen Pfs25 and/or the gamete/gametocyte surface protein Pf230C0, or variants or fragments thereof.2. The mixture according to claim 1 , wherein the domain of PfCSP is the TSR-domain of PfCSP.3. The mixture according to any one of to claim 1 , wherein the domain of PfTRAP is the TSR-domain of PfTRAP.4Plasmodium falciparum. The mixture according to any one of to claim 1 , wherein the blood stage antigens comprise at least a further blood stage antigen.5. The mixture according to any one of to claim 1 , wherein the pre-erytrocytic antigens are comprised in a recombinant fusion protein.6. The mixture according to claim 5 , ...

ANTI-MALARIA COMPOSITIONS AND METHODS

Multilayer films comprise polypeptide epitopes from , specifically a circumsporozoite CIS43 epitope and one or more of circumsporozoite T1, B or T* epitope. The multilayer films are capable of eliciting an immune response in a host upon administration to the host. The multilayer films can include at least one designed peptide that includes one or more polypeptide epitopes from a protozoan. 1. A composition comprisinga multilayer film comprising a plurality of oppositely charged polyelectrolyte layers,{'i': 'Plasmodium falciparum', 'sup': 'M', 'wherein one of the polyelectrolyte layers in the multilayer film comprises an antigenic polyelectrolyte, wherein the antigenic polyelectrolyte comprises a circumsporozoite CIS43 epitope and one or more of T1, B, T* and T*epitopes covalently linked to the antigenic polyelectrolyte;'}wherein the polyelectrolytes in the multilayer film comprise a polycationic material or a polyanionic material having a molecular weight of greater than 1,000 and at least 5 charges per molecule.2Plasmodium falciparum. The composition of claim 1 , wherein the antigenic polyelectrolyte comprises two of the circumsporozoite T1 claim 1 , B claim 1 , T* and T*epitopes.3Plasmodium falciparum. The composition of claim 1 , wherein the antigenic polyelectrolyte comprises all three of the circumsporozoite T1 claim 1 , B claim 1 , T* and T*epitopes.4. The composition of claim 1 , wherein the first antigenic polyelectrolyte is a polypeptide.5. The composition of claim 1 , wherein the multilayer film further comprises a TLR ligand.6. The composition of claim 1 , wherein the multilayer film is deposited on a core particle.7. The composition of claim 6 , wherein the antigenic polyelectrolyte is in the outermost layer of the multilayer film.8. A composition comprisinga multilayer film comprising a plurality of oppositely charged polyelectrolyte layers,{'i': 'Plasmodium falciparum', 'wherein a first polyelectrolyte layer in the multilayer film comprises a first ...

NOVEL ANTIGEN FOR USE IN MALARIA

The present invention provides polypeptides useful as antigens expressed at the pre-erythrocytic stage of the malaria parasite. The antigens can be utilized to induce an immune response and sterile protection against malaria in a mammal by administering the antigens in vaccine formulations or expressing the antigens in DNA or other recombinant protein expression systems delivered as a vaccine formulation. 113-. (canceled)14. A method of inducing an immune response against malaria in a subject , comprising administering to the subject an immunogenic composition comprising: wherein the recombinant polypeptide comprises SEQ ID NO:3, or a recombinant polypeptide that comprises at least 10 contiguous amino acids of SEQ ID NO:3 and has at least 85% sequence identity with SEQ ID NO:3;', '(b) a pharmaceutical acceptable carrier; and', '(c) an adjuvant., '(a) a recombinant polypeptide;'}15. The method of claim 14 , wherein the recombinant polypeptide comprises at least 10 contiguous amino acids of SEQ ID NO:3 and has at least 92% sequence identity with SEQ ID NO:3.16. The method of claim 14 , wherein the recombinant polypeptide comprises SEQ ID NO:3.17Plasmodium falciparum. The method claim 14 , wherein the recombinant polypeptide is an E140 antigen of a strain.18. The method of claim 17 , wherein the strain selected from the group consisting of 3D7 claim 17 , UGT5.1 claim 17 , 7G8 claim 17 , Mali claim 17 , UGPA claim 17 , HB3 claim 17 , Santa Lucia claim 17 , IGH-CR14 claim 17 , FCH/4 claim 17 , NF135/5-C10 claim 17 , Tanzania claim 17 , FVO claim 17 , and Dd2.19. The method of claim 14 , wherein the recombinant polypeptide is produced using an expression vector for prokaryotic or eukaryotic expression.20. The method of claim 19 , wherein the expression vector is a plasmid claim 19 , replicating viral vector claim 19 , or non-replicating viral vector.21. The method of claim 19 , wherein the expression vector is a DNA plasmid claim 19 , baculovirus claim 19 , rVSV claim 19 ...

INFECTIOUS PLASMODIUM SPOROZOITES GROWN IN VITRO

The application is directed to in vitro-reared sporozoites of human host range wherein sporogony from gametocyte stage to sporozoite stage is external to mosquitoes, and methods of producing the same. Provided herein are in vitro-reared infectious sporozoites (SPZ) of human host range, particularly and wherein sporogony from gametocyte stage to sporozoite stage is external to mosquitoes, and methods of producing the same. 1PlasmodiumPlasmodium. In vitro-reared infectious sporozoites of human host range , wherein sporogony from gametocyte stage to sporozoite stage is external to mosquitoes , and wherein the in vitro-reared infectious sporozoites of human host range are genetically attenuated.2Plasmodium. The genetically attenuated in vitro-reared infectious sporozoites of human host range of claim 1 , which are absent any mosquito material.3PlasmodiumPlasmodium. The genetically attenuated in vitro-reared infectious sporozoites of human host range of claim 1 , which are at least 90% as infectious of human hepatocytes as sporozoites of human host range reared in a mosquito.4Plasmodium. The genetically attenuated in vitro-reared sporozoites of human host range of claim 1 , which are aseptic.5. (canceled)6PlasmodiumPlasmodiumP. falciparum.. The genetically attenuated in vitro-reared sporozoites of human host range of claim 1 , wherein the species of said sporozoites is7Plasmodium. A culture comprising the genetically attenuated in vitro-reared sporozoites of human host range of .8Plasmodium. The culture of claim 7 , wherein said genetically attenuated in vitro-reared parasites of human host range have reached sporozoite stage of development.9PlasmodiumPlasmodium. The culture of claim 8 , wherein said sporozoite stage of genetically attenuated in vitro-reared parasites of human host range are at least 90% as infectious of human hepatocytes as human host range sporozoites of the same species reared in a mosquito.10. The culture of claim 7 , which is aseptic.11. (canceled) ...

PLASMODIUM FALCIPARUM AND PLASMODIUM VIVAX VACCINE

The present invention relates to a vaccine V comprising (A) at least one isolated polypeptide strand P comprising or consisting of at least nine consecutive amino acid moieties of the repetitive organellar protein, putative of Plasmodium falciparum or the hypothetical protein PVNG_04523 of or a polynucleotide strand encoding for such polypeptide; and (B) at least one pharmaceutically acceptable carrier or excipient. Furthermore, the present invention refers to an antibody binding to the repetitive organellar protein,putative of the hypothetical protein PVNG_04523 of or a polynucleotide strand encoding therefor, to a method of generating such antibody and uses thereof. 123-. (canceled)24. A vaccine V comprising:(A) at least one isolated polypeptide strand P comprising or consisting of at least nine consecutive amino acid moieties of SEQ ID NO: 2, of SEQ ID NO: 3 or of SEQ ID NOs: 2 and 3, or a polynucleotide strand encoding for said polypeptide strand P; and(B) at least one pharmaceutically acceptable carrier or excipient.25. The vaccine V of claim 24 , wherein the isolated polypeptide strand P is obtained from heterologous expression.26. The vaccine V of claim 24 , wherein the isolated polypeptide strand P is obtained from heterologous expression in bacterial or eukaryotic cells.27. The vaccine V of claim 24 , wherein the at least one isolated polypeptide strand P comprises or consists of at least nine consecutive amino acid moieties of a sequence having at least 80% sequence homology to a peptide sequence selected from the group consisting of SEQ ID NO: 2 claim 24 , SEQ ID NO: 3 claim 24 , SEQ ID NO: 7 claim 24 , SEQ ID NO: 8 claim 24 , SEQ ID NO: 9 claim 24 , SEQ ID NO: 10 claim 24 , SEQ ID NO: 11 claim 24 , SEQ ID NO: 12 claim 24 , SEQ ID NO: 13 claim 24 , SEQ ID NO: 14 claim 24 , SEQ ID NO: 15 claim 24 , and SEQ ID NO: 16.28. The vaccine V of claim 24 , wherein said vaccine V comprises an adjuvant supporting immunologic stimulation.29. The vaccine V of claim 24 ...

MODIFIED CATIONIC LIPOSOME ADJUVANTS

The present invention relates to the use of vaccines with adjuvants comprising cationic liposomes where neutral lipids has been incorporated into the liposomes to change the gel-liquid phase transition and thereby modifying the IgG sub-type response and enhancing the CD8 response of the liposomal adjuvant. This technology can be used to increase the production of IgG2 antibodies. This sub-type of antibodies (IgG2 in mice corresponding to IgG3 in humans) have been shown to selectively engage Fc activatory receptors on the surface of innate immune cells leading to enhanced proinflammatory responses and thereby a more efficient immune response with higher levels of protection in animal models of e.g. malaria and . The use of adjuvants which selectively give rise to higher levels of IgG2 antibodies will improve the effect of vaccines e.g. against intracellular infections. Furthermore the technology can be used to induce a CD8 response which has been reported to improve the effect of vaccines against e.g. HPV, HIV, influenza and cancer have been shown to selectively engage Fc activatory receptors on the surface of innate immune cells leading to enhanced proinflammatory responses and thereby a more efficient immune response with higher levels of protection in animal models of e.g. malaria and . The use of adjuvants which selectively give rise to higher levels of IgG2 antibodies will improve the effect of vaccines e.g. against intracellular infections. Furthermore the technology can be used to induce a CDS response which has been reported to improve the effect of vaccines against e.g. HPV, HIV, influenza and cancer. 1. A method for modifying the gel-liquid crystalline phase transition temperature (Tm) of the cationic liposomes of adjuvants comprising cationic liposomes stabilized with glycolipids by incorporating 1-Acyl-2-Acyl-sn-Glycero-3-Phosphocholine (DxPC) , wherein 1-Acyl and 2-Acyl each is independently a long chain fatty acid containing from 12 to 24 carbon (C) ...

ANTIPLASMODIAL COMPOUNDS

Novel compositions and methods for the treatment and prevention of malaria are disclosed herein. 1. A composition comprising one or more enumerated agents or a derivative thereof , or pharmaceutically acceptable salt of the foregoing.3. The composition of claim 1 , further comprising one or more conjunctive agentsor a derivative thereof, or pharmaceutically acceptable salt of the foregoing.4. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'an effective amount of the composition ; and'}a pharmaceutically acceptable carrier.5. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00002', 'claim 2'}, 'an effective amount of the composition of ; and'}a pharmaceutically acceptable carrier.6. A method for treating or preventing malaria in a subject comprising administering to a subject in need thereof an effective amount of a composition of .8. A method for treating a condition in a subject in need claim 1 , the method comprising administering to the subject an effective amount of a composition comprising one or more enumerated agents wherein the condition comprises of a symptom of malaria.10. The method of claim 8 , wherein the composition further comprises a pharmaceutically acceptable carrier.11. The method of claim 8 , further comprising co-administering a conjunctive anti-malarial agent to the subject.12F. plasmodium. The method of claim 8 , wherein treating treating comprises killing or arresting the growth of in a subject in need thereof.13. The composition of claim 1 , further comprising an anti-malarial conjunctive agent.14. A composition of claim 13 , wherein the one or more enumerated agents comprises an HDAC inhibitor or a peptaibol.15. The composition of claim 13 , wherein the one or more enumerated agents comprises a peptaibol.17. The method of claim 16 , wherein composition further comprises a pharmaceutically acceptable carrier.18. The method of claim 16 , further comprising co-administering a ...

TREATMENT AND PREVENTION OF MALARIA

There are provided antigens, vectors encoding the antigens, and antibodies and other binding compounds to the antigens and uses thereof in the prevention or treatment of malaria. In particular, compositions are provided comprising a Reticulocyte-binding protein Homologue 5 (PfRH5) antigen having at least 90% identity with SEQ ID NO: 1, or a fragment thereof; or which comprise a viral vector that expresses PfRH5 antigen having at least 90% identity with SEQ ID NO: 2, or a fragment thereof. 14-. (canceled)5. A viral vector or DNA plasmid that expresses PfRH5 antigen having at least 90% identity with SEQ ID NO:2 or a fragment thereof that has a common antigenic cross-reactivity with said PfRH5 antigen.6. The viral vector or DNA plasmid of that expresses PfRH5 antigen having at least 90% identity with amino acid residues 34 to 534 of SEQ ID NO:2 or a fragment thereof that has a common antigenic cross-reactivity with said PfRH5 antigen.7. The viral vector or DNA plasmid of claim 5 , wherein the viral vector or DNA plasmid expresses one or more antigens selected from the group consisting of PfAMA1 claim 5 , PfEBA175 claim 5 , PfRH2a claim 5 , PfRH2b and PfRH4 claim 5 , or a fragment thereof.8. The viral vector or DNA plasmid of claim 5 , further comprising a viral vector or DNA plasmid that expresses one or more antigens selected from the group consisting of PfAMA1 claim 5 , PfEBA175 claim 5 , PfRH2a claim 5 , PfRH2b and PfRH4 claim 5 , or a fragment thereof.9. The viral vector of claim 5 , wherein the viral vector is a human or simian adenovirus claim 5 , or a pox virus.10. The viral vector of claim 9 , wherein the viral vector is an AdHu5 claim 9 , AdCh63 or modified vaccinia Ankara (MVA) vector.11. The DNA plasmid of claim 5 , wherein the DNA vector is capable of expression in a mammalian expression system.1219-. (canceled)20. A vaccine composition comprising the vector and/or DNA plasmid of .2128-. (canceled) This application is a divisional of allowed U.S. ...

ANTI-MALARIA COMPOSITIONS AND METHODS

Described herein are multilayer films that include modified polypeptide epitopes from , specifically a modified T* epitope. The multilayer films are capable of eliciting an immune response in a host upon administration to the host. The multilayer films can include at least one designed peptide that includes the modified T* polypeptide epitope from a protozoan. 1. An isolated peptide comprising the sequence of SEQ ID NO: 5.2. The isolated peptide of claim 1 , further comprising the sequence of SEQ ID NO: 1 claim 1 , SEQ ID NO: 2 claim 1 , or both.3. The isolated peptide of claim 1 , wherein the isolated peptide is covalently linked to a polycationic material or a polyanionic material having a molecular weight of greater than 1 claim 1 ,000 and at least 5 charges per molecule.4. The isolated peptide of claim 1 , wherein the isolated peptide is covalently linked to one or two surface adsorption regions at the C-terminus and/or the N-terminus of the polypeptide claim 1 , wherein at least one of the surface adsorption regions comprises five or more negatively or positively charged amino acid residues.5. The isolated peptide of claim 1 , comprising SEQ ID NO: 12 or SEQ ID NO: 13.6. A composition comprisinga first multilayer film comprising a plurality of oppositely charged polyelectrolyte layers, wherein one of the polyelectrolyte layers in the multilayer film comprises a first antigenic polyelectrolyte,{'i': 'Plasmodium falciparum', 'wherein the first antigenic polyelectrolyte comprises a modified circumsporozoite T* epitope of SEQ ID NO: 5, and'}wherein the polyelectrolytes in the multilayer film comprise a polycationic material or a polyanionic material having a molecular weight of greater than 1,000 and at least 5 charges per molecule.7. The composition of claim 6 , wherein the first multilayer film is deposited on a core nanoparticle or core microparticle claim 6 , or is in the form of a nanocapsule or microcapsule prepared by dissolving the core nanoparticle or core ...

Functional screening of antigenic polypeptides-use for the identification of antigens eliciting a protective immune response and for the selection of antigens with optimal protective activity

The invention is in the field of functional screening of protective antigens against pathogens in particular against pathogens such as parasites, bacteria, viruses or protective antigens of cancer cells in order to identify antigens suitable for the elicitation of a protective immune response in a host, and/or to optimize antigen design, in particular to define suitable antigen combinations for a protective immune response. The invention thus involves using a lentiviral vaccine platform for induction of a specific cellular or humoral response against assayed antigens on one hand, and using a fast and reproducible assay for the evaluation of the induced protective effect after challenge.

Multiple malaria pre-erythrocytic antigens and their use in the elicitation of a protective immune response in a host

The invention relates to antigenic polypeptides identified through the use of a specifically devised functional immunization screening assay. In particular, the invention relates to antigenic polypeptides of malaria parasites wherein said antigenic polypeptides that exhibit a protective effect, especially that of eliciting a protective immune response in a host against challenge by sporozoites. The invention relates to a combination of compounds, comprising at least 2 distinct active ingredients wherein each active ingredient consists of an antigenic polypeptide of a parasite, a polynucleotide encoding the antigenic polypeptide, or a vector, in particular a viral vector, especially a lentiviral vector, expressing such antigenic polypeptide of a Plasmodium parasite, wherein one antigenic polypeptide is the circumsporozoite protein (CSP) or a polypeptidic derivative thereof and another antigenic polypeptide is either protein Ag40 (11-09) or protein Ag45 (11-10). 141-. (canceled)42PlasmodiumPlasmodium. A combination of compounds , comprising at least 2 distinct active ingredients wherein each active ingredient consists of an antigenic polypeptide of a parasite , a polynucleotide encoding the antigenic polypeptide , or a vector , in particular a viral vector , especially a lentiviral vector , expressing such antigenic polypeptide of a parasite , wherein one antigenic polypeptide is the circumsporozoite protein (CSP) or a polypeptidic derivative thereof and another antigenic polypeptide is either protein Ag40 (11-09) having the sequence of SEQ ID No. 67 , 68 , 70 , 71 , 73 or 74 , or a polypeptidic derivative thereof or protein Ag45 (11-10) having the sequence of SEQ ID No. 76 , 77 , 79 , 80 , 82 or 83 or a polypeptidic derivative thereof , provided each polypeptidic derivative keeps essentially the protective properties of the antigen from which it derives.43PlasmodiumPlasmodium. A combination of compounds according to claim 42 , which further comprises as active ...

VACCINES AGAINST PREGNANCY-ASSOCIATED MALARIA

The present invention relates to combinations of polypeptides or of polynucleotides corresponding to a specific region of the N-terminal portion of the VAR2CSA protein of different parasitic families or lines of , and to their use in the prevention of pregnancy-associated malaria. The invention also relates to immunogenic compositions and to vaccines useful for preventing malaria in pregnant women. 123-. (canceled)24. A vaccine or immunogenic composition for the treatment or prevention of pregnancy-associated malaria , said vaccine or immunogenic composition comprising a combination of at least two isolated or purified polypeptides , wherein:{'i': 'Plasmodium falciparum', 'the first isolated or purified polypeptide consists of the NTS-DBL1x-Id1-DBL2x region or the Id1-DBL2x region of the VAR2CSA protein of a first parasitic family of whose VAR2CSA protein is characterized by an Id1 interdomain that has as sequence the consensus sequence SEQ ID NO: 11 or that is encoded by the consensus sequence SEQ ID NO: 13; and'}{'i': 'Plasmodium falciparum', 'the second isolated or purified polypeptide consists of the NTS-DBL1x-Id1-DBL2x region or the Id1-DBL2x region of the VAR2CSA protein of a second parasitic family of whose VAR2CSA protein is characterized by an Id1 interdomain that has as sequence the consensus sequence SEQ ID NO: 12 or that is encoded by the consensus sequence SEQ ID NO: 14.'}25Plasmodium falciparum. The vaccine or immunogenic composition according to claim 24 , wherein the second parasitic family of comprises the parasitic line FCR3 and the parasitic line 3D7.26. The vaccine or immunogenic composition according to claim 25 , wherein said vaccine or immunogenic composition consists of three isolated or purified polypeptides claim 25 , wherein:{'i': 'Plasmodium falciparum', 'the first isolated or purified polypeptide consists of the NTS-DBL1x-Id1-DBL2x region or the Id1-DBL2x region of the VAR2CSA protein of the parasitic family of whose VAR2CSA protein is ...

NOVEL METHODS FOR INDUCING AN IMMUNE RESPONSE

Methods and uses are provided for inducing an immune response comprising at least two administrations of an immunogenic composition, wherein a lower dose is given in the second administration than in the first administration, and wherein the second administration may be unadjuvanted. 1. A method for inducing an immune response in a human subject comprising administering to the subject:(a) a first immunogenic composition comprising one or more antigens and a first adjuvant, and(b) a second immunogenic composition comprising one or more antigens and a second adjuvant, (i) the time interval between administration of the first immunogenic composition and the second immunogenic composition is between 1 and 24 months,', '(ii) the first and second immunogenic compositions have at least one antigen in common,', '(iii) the first and second adjuvants comprise a component selected from a TLR agonist and an immunologically active saponin, and have at least one of these two components in common,', '(iv) and wherein the second adjuvant contains a lower amount of the at least one common component than the first adjuvant, or the second immunogenic composition contains a lower amount of said common antigen than the first immunogenic composition, or both the second adjuvant contains a lower amount of the at least one common component than the first adjuvant and the second immunogenic composition contains a lower amount of said common antigen than the first immunogenic composition,, 'whereinand/orwith the proviso that the first and second immunogenic compositions do not both comprise RTS,S and QS21 and 3D-MPL associated with an oil-in-water emulsion formulation.2. The method of claim 1 , wherein first adjuvant and second adjuvant consist of the same components.3. The method of claim 1 , wherein the first and second adjuvants consist of the same components in the same relative proportions.4. (canceled)5. The method of claim 1 ,wherein the lower amount of the common component in the ...

ALGAL PRODUCED MALARIAL TRANSMISSION BLOCKING VACCINES

The present invention relates to the production of malaria transmission blocking vaccines in single-celled green algae, particularly algae of the genus , e.g., ; the immunogenic polypeptides produced and compositions comprising them; and methods for preventing, ameliorating, reducing, delaying, treating and blocking the transmission of malaria by administration of immunogenic polypeptides produced in an algal host cell. 1Plasmodium. A polynucleotide comprising a nucleic acid sequence having at least about 60% sequence identity to SEQ ID NO: 11 or SEQ ID NO:1 , wherein the nucleic acid sequence encodes a surface protein P48/45 , or immunogenic fragment thereof.23-. (canceled)4Plasmodium. A polynucleotide comprising a nucleic acid sequence having at least about 60% sequence identity to SEQ ID NO:13 or SEQ ID NO:2 , wherein the nucleic acid sequence encodes a surface protein P25 , or immunogenic fragment thereof.5Plasmodium. A polynucleotide of claim 4 , wherein the polynucleotide encodes amino acid residues 22-193 of surface protein P25.6Plasmodium. A polynucleotide of claim 4 , wherein the polynucleotide encodes a surface protein P25 claim 4 , or immunogenic fragment thereof claim 4 , having at least about 60% sequence identity to an amino sequence selected from the group consisting of SEQ ID NO:12 claim 4 , SEQ ID NO:28 SEQ ID NO:38 and SEQ ID NO:39.7Plasmodium. A polynucleotide comprising a nucleic acid sequence having at least about 60% sequence identity to SEQ ID NO:16 or SEQ ID NO:6 claim 4 , wherein the nucleic acid sequence encodes a surface protein P28 claim 4 , or immunogenic fragment thereof.89-. (canceled)10Plasmodium. A polynucleotide comprising a nucleic acid sequence having at least about 60% sequence identity to SEQ ID NO: 34 claim 4 , wherein the nucleic acid sequence encodes a surface protein P230 claim 4 , or immunogenic fragment thereof.1112-. (canceled)13Plasmodium. A polynucleotide comprising a nucleic acid sequence having at least about 60% ...

CIRCUMSPOROZOITE PROTEINS WITH INCREASED EXPRESSION IN MAMMALIAN CELLS

Mutated and/or truncated malarial circumsporozoite proteins (CSP) and associated nucleic acids that are more stable and highly expressed in mammalian cells are described. The mutated and/or truncated CSP and associated nucleic acids can be expressed to produce malaria vaccine antigens. 1. A mutant N-terminus domain (NTD) of a circumsporozoite protein (CSP) comprising a KKNSR (SEQ ID NO: 1) to SSNSA (SEQ ID NO: 4) mutation directly upstream of a SLGENDD (SEQ ID NO: 3) cleavage site and replacement of a cysteine with serine at residue 5 of the wild-type CSP protein lacking the signal peptide with serine.2. The mutant NTD of claim 1 , expressed as a fusion protein with a secondary malaria vaccine epitope.3. The mutant NTD of claim 3 , wherein the secondary malaria vaccine epitope comprises RTS claim 3 ,S; NR2C claim 3 , R2C claim 3 , the junctional epitope claim 3 , the minor epitope claim 3 , or a junctional epitope linked to the minor epitope.4. A mutant N-terminus domain (NTD) of a circumsporozoite protein (CSP) comprising a KKNSR (SEQ ID NO: 1) to SSNSS (SEQ ID NO: 2) or SSNSA (SEQ ID NO: 4) mutation directly upstream of a SLGENDD (SEQ ID NO: 3) cleavage site.5. The mutant NTD of claim 4 , comprising removal of a cysteine within the N-terminus of the CSP.6. The mutant NTD of claim 5 , wherein the cysteine is residue 5 of the wild-type CSP protein lacking the signal peptide.7. The mutant NTD of claim 5 , wherein the removal of the cysteine comprises replacing the cysteine with serine.8. The mutant NTD of claim 4 , expressed as a fusion protein with a secondary malaria vaccine epitope.9. The mutant NTD of claim 8 , wherein the secondary malaria vaccine epitope is selected from RTS claim 8 ,S; NR2C claim 8 , R2C claim 8 , the junctional epitope claim 8 , the minor epitope claim 8 , or a junctional epitope linked to the minor epitope.10. The mutant NTD of claim 8 , wherein the fusion protein comprises C5S-SAmut claim 8 , C5S-SAmut-23/4 claim 8 , C5S-SAmut-19/3 claim 8 ...

COMPOSITION AND USES THEREOF

The present invention provides a particle comprising a fusion protein, wherein the fusion protein comprises at least one NANP repeat (SEQ ID NO: 7), some or all of the C-terminus of the CS protein from and a hepatitis B surface antigen, and wherein the particle comprises no, or substantially no, free hepatitis B surface antigen protein, and uses thereof. 1Plasmodium falciparum. A particle comprising a fusion protein , wherein the fusion protein comprises at least one NANP repeat (SEQ ID NO: 7) , some or all of the C-terminus of the CS protein from and a hepatitis B surface antigen , and wherein the particle comprises no , or substantially no , free hepatitis B surface antigen protein.232.-. (canceled)33. The particle of claim 1 , wherein the hepatitis B surface antigen is an S antigen.34. The particle of comprising at least 10 NANP repeats (SEQ ID NO: 13).37Plasmodium falciparum.. The particle of claim 1 , wherein the particle comprises at least about 40% or more by mass of its proteinaceous material claim 1 , the proteinaceous material being derived from38. The particle of comprising a fusion protein comprising claim 1 , or consisting of:a sequence of SEQ ID NO: 1 (R21);a sequence of SEQ ID NO: 2 (RTS); ora sequence with at least 80%, 85%, 90%, 95%, 98%, 99% or more sequence identity with the sequence of SEQ ID NO: 1 or SEQ ID NO: 2.39Plasmodium falciparum. A fusion protein comprising at least one NANP repeat (SEQ ID NO: 7) claim 1 , some or all of the C terminus of the CS protein from claim 1 , and a hepatitis B surface antigen; or a DNA sequence encoding the fusion protein.40. The fusion protein of claim 39 , wherein the fusion protein comprises claim 39 , or consists of claim 39 , a sequence of SEQ ID NO: 1 (R21) or a sequence with at least 80% claim 39 , 85% claim 39 , 90% claim 39 , 95% claim 39 , 98% claim 39 , 99% or more sequence identity with the sequence of SEQ ID NO: 1.41Saccharomyces cerevisiaePichia pastoris. The fusion protein of claim 39 , wherein ...

Conformation-Stabilized TRAP Antigens

This invention relates to compositions and methods for eliciting an immune response against a parasite of the genus in a mammal. 1Plasmodium falciparum. A Thrombospondin-Related Anonymous Protein (TRAP) antigen , wherein the antigen sequence comprises one or more of the following (numbering relative to SEQ ID NO:5):(a) Mutation at Cysteine 55 to a non-cysteine amino acid;(b) Mutation of N-linked glycosylation sites;(c) Mutation of Ala-216/Asn-222 or Lys-224/Gln-78 to cysteine to create a TRAP that is stabilized in the open conformation;(d) Mutation of Asn-213/Ala-233, Ala-216/Phe-230, or Met-231/Gln-78 to cysteine to create a TRAP that is stabilized in the closed conformation;(e) Deletion of N-terminal and/or C-terminal residues to create a TRAP fragment that is stabilized in the closed conformation comprising V47-V238;(f) Deletion of N-terminal and/or C-terminal residues to create a TRAP fragment that is stabilized in the open conformation comprising V47-M231.2P. falciparum. The antigen of claim 1 , wherein the sequence is a mutated TRAP sequence that is at least 80% identical to SEQ ID NO:5.3. The antigen of claim 1 , wherein the mutation at Cys55 is to Glycine claim 1 , Serine claim 1 , or Alanine.4. The antigen of claim 1 , wherein the mutation of an N-linked glycosylation site is a mutation of N or (S/T) in the carbohydrate-encoding sequence N-X-(S/T).5. The antigen of claim 4 , wherein the mutation is N132S claim 4 , S477N claim 4 , and/or N483S.6Plasmodium vivax. A Thrombospondin-Related Anonymous Protein (TRAP) antigen claim 4 , wherein the antigen sequence comprises one or more of the following (numbering relative to SEQ ID NO:6):(a) Mutation of N-linked glycosylation sites;(b) Mutation of Ser-212/Glu-218, Val-220/Ser-74 to cysteine to create a TRAP that is stabilized in the open conformation;(c) Mutation of Ser-212/Phe-226, Ile-223/Met-67, Ile-227/Ser-74 to cysteine to create a TRAP that is stabilized in the closed conformation;(d) Deletion of N-terminal ...

COMPOSITIONS AND METHODS OF ENHANCING IMMUNE RESPONSES TO EIMERIA OR LIMITING EIMERIA INFECTION

Vaccine vectors and methods of using the vaccine vectors to enhance the immune response to an Apicomplexan parasite and reduce the morbidity or mortality associated with subsequent infection are provided herein. The vaccine vectors include a polynucleotide encoding a Rhomboid polypeptide and optionally include an immune-stimulatory polypeptide suitably expressed on the surface of the vaccine vector. 1. A vaccine vector comprising a first polynucleotide sequence encoding an apicomplexan rhomboid polypeptide expressed on the surface of the vaccine vector , wherein the Rhomboid polypeptide consists of a polypeptide having greater than 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO: 3 , SEQ ID NO: 37 , an immunogenic fragment of SEQ ID NO: 3 comprising at least 14 amino acids of SEQ ID NO: 3 , an immunogenic fragment of SEQ ID NO: 3 comprising amino acids 7-16 of SEQ ID NO: 3 , an immunogenic fragment of SEQ ID NO: 37 comprising at least 14 amino acids of SEQ ID NO: 37 , and an immunogenic fragment of SEQ ID NO: 37 comprising amino acids 7-16 or 20-32 of SEQ ID NO: 37.2. The vaccine vector of further comprising a second polynucleotide sequence encoding an immunostimulatory polypeptide claim 1 , wherein the immunostimulatory polypeptide is expressed on the surface of the vaccine vector claim 1 , and wherein an immunostimulatory polypeptide comprises a polypeptide capable of stimulating an immune response.3. The vaccine vector of claim 2 , wherein the immunostimulatory polypeptide comprises an HMGB1 polypeptide.4. The vaccine vector of claim 3 , wherein the HMGB1 polypeptide comprises a polypeptide selected from the group consisting of SEQ ID NOs: 15-23 claim 3 , a polypeptide having at least 95% sequence identity to SEQ ID NO: 15-23 and combinations thereof.525. The vaccine vector of claim 2 , wherein the immunostimulatory polypeptide comprises a CD154 polypeptide capable of binding CD40 claim 2 , the CD154 polypeptide ...

ANTI-MALARIAL COMPOSITIONS

This disclosure provides antibodies that are useful for preventing and/or treating malaria. The epitope to which the antibodies bind is in close proximity to the conserved proteolytic cleavage site of circumsporozoite protein (CSP), and the antibodies provided in this disclosure can prevent cleavage and inhibit sporozoites from invading the liver. 1. An isolated antibody which: [{'sub': H', 'H', 'H, '(1) an immunoglobulin heavy chain variable region, comprising a first heavy chain complementarity determining region (CDR) comprising the amino acid sequence SEQ ID NO:1; a second CDRcomprising the amino acid sequence SEQ ID NO:2; and a third CDRcomprising the amino acid sequence SEQ ID NO:3; and'}, {'sub': L', 'L', 'L, '(2) an immunoglobulin light chain variable region comprising a first light chain complementarity determining region (CDR) comprising the amino acid sequence SEQ ID NO:4; a second CDRcomprising the amino acid sequence SEQ ID NO:5; and a third CDRcomprising the amino acid sequence SEQ ID NO:6;'}], '(a) comprisesor(b) comprises the complementarity determining regions of the immunoglobulin heavy and light chains of the antibody deposited under Accession No. MRA-1242.2. The isolated antibody of claim 1 , which is an scFv antibody.3. The isolated antibody of claim 1 , which is humanized.47-. (canceled)8. A pharmaceutical composition claim 1 , comprising the antibody of and a pharmaceutically acceptable carrier.9Plasmodium. A method of protecting an individual against a infection claim 1 , comprising administering to an individual in need thereof an effective amount of a pharmaceutical composition comprising the antibody of .10. The method of claim 9 , further comprising administering to the individual a malarial antigen.11. A method of treating malaria claim 1 , comprising administering to an individual in need thereof an effective amount of a pharmaceutical composition comprising the antibody of .12. The method of claim 11 , further comprising administering ...

VACCINE COMPRISING AMA1 AND RON2

Disclosed is a vaccine comprising an immunogenic composition comprising a complex of AMA1 and RON2 (or a fragment thereof), which elicits an immune response to a species in a subject upon administration. The resulting immune response is sufficient to impede or prevent infection by a species. 1. A vaccine comprising: i) an immunogenic composition comprising a complex of AMA1 and RON2; and ii) at least one adjuvant and/or at least one physiologically acceptable carrier.2. A vaccine comprising: i) an immunogenic composition comprising a complex of: a) AMA1; and b) RON2 and/or a fragment thereof; and ii) at least one adjuvant and/or at least one physiologically acceptable carrier.3Plasmodium. The vaccine of claim 2 , wherein the composition elicits an immune response to a species in a subject upon administration to the subject.443Plasmodium. The vaccine of claim claim 2 , wherein the immune response is sufficient to impede or prevent infection by a species.5. The vaccine of claim 2 , wherein the vaccine is for the treatment of or protection from erythrocytic and/or pre-erythrocytic malaria infection in a subject.6. The vaccine of claim 5 , wherein the treatment manifests itself in the subject as parasitemia being under control and/or the infection being cleared.7PlasmodiumPlasmodium falciparum, Plasmodium knowlesi, Plasmodium vivax, Plasmodium yoelii, Plasmodium malariae, Plasmodium ovale, Plasmodium brasilianum, Plasmodium cynomulgi, Plasmodium inui, Plasmodium rhodiani, Plasmodium schwetzi, Plasmodium semiovalePlasmodium simium.. The vaccine of claim 3 , wherein the species is selected from the group consisting of claim 3 , and8. A method of protecting a subject from erythrocytic malaria infection comprising administering the vaccine of to the subject in an amount effective to stimulate an immune response claim 2 , thus protecting the subject from erythrocytic malaria infection.9. A method of protecting a subject from pre-erythrocytic malaria infection comprising ...

PHARMACEUTICAL COMPOSITIONS COMPRISING ATTENUATED PLASMODIUM SPOROZOITES AND GLYCOLIPID ADJUVANTS

Disclosed herein are pharmaceutical compositions comprising sporozoite-stage parasites and compatible glycolipid adjuvants useful in vaccines for preventing or reducing the risk of malaria. In particular, human host range and analogues of α-galactosylceramide (α-GalCer), a ligand for natural killer T (NKT) cells, are combined in pharmaceutical compositions, which are useful as vaccines against malaria. Methods of use are also provided. 137-. (canceled)39. The method of claim 38 , wherein said one or more doses comprise no more than 150 claim 38 ,000 sporozoites.40. The method of claim 39 , wherein said one or more doses comprise no more than 50 claim 39 ,000 sporozoites.41. The method of claim 40 , wherein said one or more doses comprise no more than 25 claim 40 ,000 sporozoites.42. The method of claim 38 , wherein no more than 3 doses are administered.43. The method of claim 42 , wherein no more than 2 doses are administered.44. The method of claim 43 , wherein no more than 1 dose is administered.45P. falciparum, P. vivax, P. ovale, P. knowlesi,P. malariae.. The method of claim 38 , wherein said species are selected from the group consisting of: and46P. falciparum.. The method of claim 38 , wherein said species comprises47. The method of claim 38 , wherein said pharmaceutical composition is administered by an intravenous claim 38 , intramuscular claim 38 , intradermal claim 38 , or subcutaneous route.48. The method of claim 47 , wherein said pharmaceutical composition is administered by an intravenous route.49. The method of claim 38 , wherein said glycolipid adjuvant is administered by an intravenous claim 38 , intramuscular claim 38 , intradermal claim 38 , or subcutaneous route.50. The method of claim 38 , wherein the co-administration is sequential.51. The method of claim 38 , wherein the co-administration is concurrent.52. The method of claim 51 , wherein said glycolipid adjuvant and said pharmaceutical composition are admixed prior to co-administration.53. ...

MALARIA ANTIGENS AND METHODS OF USE

The invention is directed to a composition comprising one or more polypeptides or one or more nucleic acid sequences that can induce a protective immune response against species that infect humans. The invention also is directed to a method of using such compositions to induce a protective immune response against a parasite in a mammal. 197.-. (canceled)98. A composition comprising a pharmaceutically acceptable carrier and a vector encoding one or more isolated polypeptides , wherein each of the one or more isolated polypeptides comprises: (a) an amino acid sequence comprising at least 20 contiguous amino acid residues of the sequence MKKDREPIDEDEMRITSTGRMTNYVNYGAKILG (SEQ ID NO: 20) , (b) an amino acid sequence comprising at least 20 contiguous amino acid residues of the sequence KIKATGNAIGKAVTLAEIIKRRFKGLHQIT (SEQ ID NO: 21) , or (c) an amino acid sequence comprising SEQ ID NO: 22.99. The composition of claim 98 , wherein the composition comprises an isolated polypeptide comprising at least 20 contiguous amino acid residues of the sequence MKKDREPIDEDEMRITSTGRMTNYVNYGAKILG (SEQ ID NO: 20).100. The composition of claim 99 , wherein the composition comprises an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 20.101. The composition of claim 98 , wherein the composition comprises an isolated polypeptide comprising at least 20 contiguous amino acid residues of the sequence KIKATGNAIGKAVTLAEIIKRRFKGLHQIT (SEQ ID NO: 21).102. The composition of claim 101 , wherein the composition comprises an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 21.103. The composition of claim 98 , wherein the composition comprises an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 22.104. The composition of claim 103 , wherein the isolated polypeptide comprises the amino acid sequence of KDAGYQPPLDEKYVKEMXPEEIVN (SEQ ID NO: 23) claim 103 , wherein X is a serine (S) residue or a threonine (T) residue.105. The composition of ...

VACCINES AGAINST MALARIA TRANSMISSION

The invention pertains to methods and vaccines suitable for preventing or reducing malaria transmission. The vaccines block the interaction between α-tubulin from a malarial parasite and FREP-1 from the mid-gut of a malaria carrier mosquito, for example, 1. A method for preventing or reducing malaria transmission through a mosquito , comprising administering to the mosquito a composition comprising a malaria transmission-blocking agent , the malaria transmission-blocking agent comprising an antibody or antigen binding fragment thereof that specifically binds an antigen of a malaria parasite.2. The method according to claim 1 , the mosquito being infected with the malaria parasite.3P. berghei, P. vivax, P. knowlesi, P. malariae, P. falciparumP. ovale.. The method according to claim 1 , the malarial parasite being claim 1 , or4. The method according to claim 1 , the composition being an anti-serum claim 1 , or blood sample.5. The method according to claim 1 , wherein the antibody or antigen binding fragment thereof blocks the interaction between a mid-gut peritrophic matrix (PM) protein of the mosquito and the antigen from the malaria parasite.6. The method according to claim 5 , the mid-gut PM protein of the mosquito being FREP-1.7. The method according to claim 1 , the antigen being selected from FBP1 (Hsp70) claim 1 , FBP3 (α-tubulin 1) claim 1 , FBP5 (U1 snRNA associated protein) claim 1 , and FBP6 (Exported protein IBIS1).8Plasmodium. The method according to claim 1 , the antigen being α-tubulin-1.9Plasmodium. The method according to claim 8 , the α-tubulin-1 comprising a sequence selected from SEQ ID NOs: 2-6 and sequences sharing at least 90% identity to any of SEQ ID NOs: 2-6.10Plasmodium. The method according to claim 1 , wherein the antibody or antigen binding fragment thereof specifically binds to YEADY (SEQ ID NO: 7) claim 1 , ASRANDDA (SEQ ID NO: 42) claim 1 , MFSAV (SEQ ID NO: 43) claim 1 , NFCCWPSP (SEQ ID NO: 44) claim 1 , and/or VFSRMDQK (SEQ ID NO: ...

NYVAC-BASED PLASMODIUM MALARIA VACCINE

The disclosure generally provides a WRrNYVAC comprising multiple antigens from different stages of a malaria parasite () life cycle, methods for producing them, immunogenic vaccine formulations comprising WRrNYVAC, such as containing formulations (WRPvrNYVAC) and containing formulations (WRPfrNYVAC) and methods for the prevention and/or treatment of malaria infections and poxvirus infections. 1. A method of eliciting a protective immune response in a subject against malaria infection , comprising administering to the subject an effective amount of a recombinant NYVAC (rNYVAC) virus capable of expressing a malaria antigen gene , wherein the malaria antigen gene is under the control of a compact synthetic early-late promoter comprising the nucleotide sequence of SEQ ID NO: 1 and is inserted into a region of the NYVAC viral genome selected from the group consisting of A26L , A56R , I4L , J2R , B13/B14R , and C7L-K1L , and wherein the malaria antigen gene encodes a malaria antigen selected from the group consisting of a pre-erythrocytic stage antigen , a blood stage antigen , or a transmission blocking stage antigen.2. The method of claim 1 , wherein administering the rNYVAC virus elicits a protective immune response against a poxvirus infection in the subject.3. The method of claim 1 , wherein the rNYVAC virus is capable of expressing two or more malaria antigen genes encoding malaria antigens of different developmental stages.4. The method of claim 1 , wherein two or more recombinant NYVAC viruses are administrated claim 1 , and wherein the two or more rNYVAC viruses are capable of expressing two or more malaria antigen genes encoding malaria antigens of different developmental stages.5. The method of claim 4 , wherein the rNYVAC virus is administered claim 4 , either in combination or separately claim 4 , via a route selected from the group consisting of scarification claim 4 , intramuscular injection claim 4 , intradermal injection claim 4 , subcutaneous injection ...

POLYSACCHARIDE COMPOSITIONS AND METHODS OF USE

The invention relates, in part, to the use of compositions of poly N-acetylated glucosamine (PNAG) and antibodies specific to PNAG in the prevention and treatment of infections by certain PNAG-positive pathogens and in detection (including diagnostic) methods. 3. The method of claim 2 , wherein the isolated polysaccharide is conjugated to the carrier through a linker.4. The method of or claim 2 , wherein the carrier is a peptide carrier.5. The method of any one of the foregoing claims claim 2 , wherein less than 30% claim 2 , less than 20% claim 2 , less than 10% claim 2 , or less than 5% of R groups are —NH—CO—CH.6. The method of any one of the foregoing claims claim 2 , wherein none of the R groups is —NH—CO—CH.76. The method of any one of - claims 1 , wherein n is at least 15 claims 1 , at least 20 claims 1 , at least 50 claims 1 , at least 100 claims 1 , at least 200 claims 1 , at least 300 claims 1 , at least 400 or at least 500.86. The method of any one of - claims 1 , wherein the isolated polysaccharide has a molecular weight of 100-500 kDa98. The method of any one of - claims 1 , wherein the non-ica/pga PNAG-positive pathogen is a non-ica/pga PNAG-positive gram-positive coccus.10S. pneumoniaStreptococcusStreptococcusEnterococcus.. The method of claim 9 , wherein the non-ica/pga PNAG-positive gram-positive coccus is claim 9 , Group A claim 9 , Group B claim 9 , or118. The method of any one of - claims 1 , wherein the non-ica/pga PNAG-positive pathogen is a non-ica/pga PNAG-positive gram-positive rod.12Listeria, Clostridium difficile, B. subtilis, M. tuberculosisM. smegmatis.. The method of claim 11 , wherein the non-ica/pga PNAG-positive gram-positive rod is claim 11 , or138. The method of any one of - claims 1 , wherein the non-ica/pga PNAG-positive pathogen is a non-ica/pga PNAG-positive gram-negative coccus or coccobacillus.14Neisseria meningitides, Neisseria gonorrhoeaeH. influenzae, HelicobacterCampylobacter.. The method of claim 13 , wherein the non-ica ...