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Небесная энциклопедия

Космические корабли и станции, автоматические КА и методы их проектирования, бортовые комплексы управления, системы и средства жизнеобеспечения, особенности технологии производства ракетно-космических систем

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Мониторинг СМИ

Мониторинг СМИ и социальных сетей. Сканирование интернета, новостных сайтов, специализированных контентных площадок на базе мессенджеров. Гибкие настройки фильтров и первоначальных источников.

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Форма поиска

Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 3571. Отображено 100.
23-02-2012 дата публикации

Human papilloma virus peptide-specific T-cell response for treatment of warts

Номер: US20120045413A1
Принадлежит: Kevin Kim, Mayumi Nakagawa, Thomas Horn

The inventors have treated human patients for warts by intralesional injection of Candida antigen to induce a delayed-type hypersensitivity response in the patients. This creates an immune response that recognizes the antigens of the human papilloma virus (HPV) found in and causing the warts. It was found that the patients showed a response to HPV type 57 L1 peptide 380-412 (a peptide consisting of amino acid residues 380-412 of the protein L1) and HPV type 57 protein E4 (E4 10-30). One embodiment of the invention provides a pharmaceutical composition comprising a polypeptide comprising (a) L1 380-412 (SEQ ID NO:3) or a fragment of at least 8 residues of SEQ ID NO:3 or (b) E4 10-30 (SEQ ID NO:4) or a fragment of at least 8 residues of E4 10-30 (SEQ ID NO:4), wherein the composition is immunogenic in humans.

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19-04-2012 дата публикации

Process for producing poxviruses and poxvirus compositions

Номер: US20120093780A1
Принадлежит: TRANSGENE SA

The present invention relates to compositions and pharmaceutical compositions comprising poxviruses and more particularly extracellular enveloped viruses. The present invention also relates to a process for producing poxviruses and poxviruses obtained thereof. Moreover, the present invention also relates to the use of said poxvirus and said composition for the preparation of a medicament.

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17-05-2012 дата публикации

Tat-Based Vaccine Compositions and Methods of Making and Using Same

Номер: US20120121636A1
Автор: David I. Cohen
Принадлежит: NANIRX Inc

A Tat-based vaccine composition comprising at least one antigen coupled to at least one immunostimulatory lentivirus trans-activator of transcription (Tat) molecule wherein the antigen is a cancer antigen an infectious disease antigen or a fragment thereof and methods to treat disease by administering the Tat-based vaccine composition. An additional Tat-based vaccine composition comprising immunostimulatory lentivirus Tat is provided.

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12-07-2012 дата публикации

Compositions and methods for treatment of cervical dysplasia

Номер: US20120177678A1
Принадлежит: Individual

The present invention provides methods of treating, protecting against, and inducing an immune response against cervical dysplasia and cancer, comprising the step of administering to a subject a recombinant Listeria strain, comprising a fusion peptide that comprises an LLO fragment and an E7 and/or E6 antigen. The present invention also provides methods for inducing an anti-E7 CTL response in a human subject and treating HPV-mediated diseases, disorders, and symptoms, comprising administration of the recombinant Listeria strain.

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07-02-2013 дата публикации

Agent for use in the topical or local treatment of cervical dysplasias

Номер: US20130034584A1
Автор: Günter Cichon
Принадлежит: Charite Universitaetsmedizin Berlin

The invention relates to an agent for treating cervical dysplasias, comprising a recombinant, genetically modified E1-deleted adenovirus replication defective in non-HPV infected cells, which is suitable for local external application in the region of the portio and the cervix uteri.

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30-05-2013 дата публикации

Biomatrix Scaffolds for Industrial Scale Dispersal

Номер: US20130137176A1

The present invention provides biomatrix scaffolds for industrial scale dispersal.

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05-09-2013 дата публикации

Papillomavirus pseudoviruses for detection and therapy of tumors

Номер: US20130230456A1
Принадлежит: National Institutes of Health NIH

Disclosed herein are methods of detecting tumors, monitoring cancer therapy, and selectively inhibiting the proliferation and/or killing of cancer cells utilizing a papilloma pseudovirus or a papilloma virus-like particle (VLP)

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23-01-2014 дата публикации

IDENTIFICATION OF A NOVEL HUMAN POLYOMAVIRUS (IPPyV) AND APPLICATIONS

Номер: US20140024017A1
Принадлежит: Individual

The invention relates to the identification of a novel human polyomavirus species (designated IPPyV) and applications derived from the identified features and properties of this virus. The IPPy virus species of the invention qualifies as a human virus, in view of the fact that it is capable of infecting a human host. Having identified a novel human polyomavirus species, IPPyV, the inventors have been able to propose means for the detection of exposure or infection by such a virus, especially detection in a biological sample previously obtained from a human host. The invention also concerns means suitable for obtaining an immune response in a host with a view to prevent the onset or the development of an infection with an IPPyV.

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10-04-2014 дата публикации

Method for producing yeast expressed hpv types 6 and 16 capsid proteins

Номер: US20140099719A1
Принадлежит: Novartis Vaccines and Diagnostics Inc

Mosaic VLPs of viral capsid proteins from different virus types are described, as are methods of making the same. Specifically, a diploid yeast strain that coexpresses the L1 and L2 capsid proteins of both HPV-6 and HPV-16 as mosaic VLPs is described. The mosaic VLPs induced the production of conformational antibodies against both L1 proteins upon administration to mice.

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07-01-2021 дата публикации

Parapoxvirus vectors

Номер: US20210000937A1
Принадлежит: TRANSGENE

The present invention is in the field of viral immunotherapy. The invention provides new pseudocowpox (PCPV) viruses, in particular recombinant PCPV, composition thereof as well as their therapeutic use for preventing or treating diseases, and, notably, proliferative diseases like cancers and restenosis and infectious diseases such as chronic ones. The present invention also provides methods for generating and amplifying such a PCPV and a method for eliciting or stimulating and/or re-orienting an immune response using such a PCPV. More specifically, the invention provides an alternative to the existing poxvirus vectors such as MVA (Modified Virus Ankara) and may be largely used for the therapeutic vaccination. 1. A pseudocowpoxvirus (PCPV) wherein said PCPV comprises at least one foreign nucleic acid inserted in its genome.2. The PCPV of claim 1 , wherein said PCPV is obtained from the wild-type TJS strain as identified by ATCC reference number ATCC VR-634™ or from a virus strain of the same or similar name or functional fragments and variants thereof.3. The PCPV of claim 1 , wherein said PCPV is further defective for a viral function encoded by the PCPV genome.4. The PCPV of claim 1 , wherein said foreign nucleic acid encodes a polypeptide selected from the group consisting of polypeptides that compensate for defective or deficient proteins in a subject claim 1 , suicide gene products claim 1 , armed gene products claim 1 , immunostimulatory polypeptides claim 1 , and antigenic polypeptides.5. The PCPV of claim 4 , wherein said immunostimulatory polypeptide is selected from the group consisting of cytokines claim 4 , chemokines claim 4 , interferons claim 4 , tumor necrosis factor claim 4 , colony-stimulating factors claim 4 , APC-exposed proteins claim 4 , agonists of immune checkpoints claim 4 , and antagonists of immune checkpoints.6. The PCPV of claim 5 , wherein said immunostimulatory polypeptide is GM-CSF or is an agonist OX40-directed antibody.7. The PCPV of ...

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02-01-2020 дата публикации

Biomatrix scaffolds

Номер: US20200002667A1

The present invention provides biomatrix scaffolds, a tissue extract enriched for extracellular matrix components and bound growth factors, cytokines and hormones, and methods of making and using same.

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04-01-2018 дата публикации

DETECTION OF NUCLEIC ACIDS FROM MULTIPLE TYPES OF HUMAN PAPILLOMAVIRUS

Номер: US20180002768A1
Принадлежит:

Nucleic acid oligonucleotide sequences are disclosed which include amplification oligomers and probe oligomers which are useful for detecting multiple types of human papillomaviruses (HPV) associated with cervical cancer. Methods for detecting multiple HPV types in biological specimens by amplifying HPV nucleic acid sequences in vitro and detecting the amplified products are disclosed. 1. A mixture of amplification oligomers in which individual oligomer sequences are selected from the group consisting of SEQ ID NO:18 to SEQ ID NO:42 , which includes the complementary oligomer sequences or RNA equivalents of the specified sequences , wherein the mixture includes:first amplification oligomers of SEQ ID Nos. 19 or 42, 21, 23, 25, 27, 29, 31, 33 and 35, and second amplification oligomers of SEQ ID Nos. 37, 38, 39, 40 and 41, or complementary oligomer sequences or RNA equivalents of the oligomer sequences;first amplification oligomers of SEQ ID Nos. 18, 20, 22, 24, 26, 28, 30, 32, 34 and 36, and second amplification oligomers of SEQ ID Nos. 37, 38, 39, 40 and 41, or complementary oligomer sequences or RNA equivalents of the oligomer sequences;first amplification oligomers of SEQ ID Nos. 19 or 42, 21, 23, 25, 27, 29, 31, 33 and 35, and second amplification oligomers of SEQ ID Nos. 38, 39, 40 and 41, or complementary oligomer sequences or RNA equivalents of the oligomer sequences; orfirst amplification oligomers of SEQ ID Nos. 18, 20, 22, 24, 26, 28, 30, 32, 34 and 36, and second amplification oligomers of SEQ ID Nos. 38, 39, 40 and 41, or complementary oligomer sequences or RNA equivalents of the oligomer sequences.2. The mixture of oligomers of claim 1 , in which one or more individual oligomers include a backbone that includes at least one 2′-methoxy RNA group claim 1 , at least one 2′ fluoro-substituted RNA group claim 1 , at least one peptide nucleic acid linkage claim 1 , at least one phosphorothioate linkage claim 1 , at least one methylphosphonate linkage or any ...

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03-01-2019 дата публикации

DETECTION OF NUCLEIC ACIDS FROM MULTIPLE TYPES OF HUMAN PAPILLOMAVIRUS

Номер: US20190002995A1
Принадлежит:

Nucleic acid oligonucleotide sequences are disclosed which include amplification oligomers and probe oligomers which are useful for detecting multiple types of human papillomaviruses (HPV) associated with cervical cancer. Methods for detecting multiple HPV types in biological specimens by amplifying HPV nucleic acid sequences in vitro and detecting the amplified products are disclosed. 13-. (canceled)4. A reaction mixture containing a detection probe oligomer for selectively detecting HPV types in group C1 in the presence of HPV types from one or more of groups A1 , A2 , B , C2 , and D , wherein the detection probe oligomer comprises:(i) a target-specific sequence consisting of a nucleotide sequence selected from the group consisting of SEQ ID NOs:13, 46, 45, complements thereof, and RNA equivalents thereof; and(ii) a detectable label.5. The reaction mixture of claim 4 , wherein the detectable label is joined directly to the oligomer.6. The reaction mixture claim 4 , wherein the detectable label is a chemiluminescent compound.7. The reaction mixture of oligomers of claim 4 , wherein the detection probe oligomer nucleotide sequence has a backbone comprising at least one 2′-methoxy RNA group.8. (canceled)9. A mixture of at least two oligomers in which individual oligomer sequences are selected from the group consisting of SEQ ID Nos. 1 to 10 claim 4 , which includes the complementary oligomer sequences or RNA equivalents of the specified sequences claim 4 , wherein the mixture includes:at least two oligomers selected from SEQ ID Nos. 2, 4, 6, 8 and 10 with a ligand moiety joined to each oligomer;oligomers of SEQ ID Nos. 2, 4, 6, 8 and 10 with a ligand moiety joined to each oligomer;at least two oligomers selected from SEQ ID Nos. 1, 3, 5, 7 and 9; oroligomers of SEQ ID Nos. 1, 3, 5, 7 and 9.10. The mixture of oligomers of claim 9 , wherein at least one oligomer comprises a backbone that includes at least one 2′-methoxy RNA group claim 9 , at least one 2′ fluoro- ...

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01-01-2015 дата публикации

RECOMBINANT VIRUS-LIKE PARTICLES ENCODED BY MULTI-GENE VECTOR

Номер: US20150004690A1
Принадлежит:

The invention describes novel virus-like particles for use as vaccines, diagnostic tools and R&D tools based on recombinant DNA and cell cultivation techniques for production. The recombinant virus-like particles of the invention are assembled by polypeptide chains that incorporate several, in particular two or more, different epitopes which are selected either (a) from different viral strains of the same virus and/or (b) from different serotypes of the same virus and/or (c) from different viral strains specific for different hosts. These epitopes are then displayed on the particle surface. 116-. (canceled)17. A single baculoviral vector encoding a recombinant virus-like particle comprising two or more different surface proteins comprising epitopes which are selected either (a) from different viral strains of the same virus and/or (b) from different serotypes of the same virus and/or (c) from different viral strains specific for different hosts.18. The baculoviral vector according to claim 17 , wherein said virus-like particle comprises three or more different epitopes or different proteins comprising epitopes19. The baculoviral vector according to claim 17 , wherein said virus-like particle comprises four or more different epitopes or different proteins comprising epitopes.20. The baculoviral vector according to claim 17 , wherein said virus-like particle comprises six claim 17 , nine or twelve different epitopes or different proteins comprising epitopes.21. The baculoviral vector according to claim 17 , wherein the epitopes are from three or more different virus strains or serotypes.22. The baculoviral vector according to claim 17 , wherein said virus-like particle further comprises B- and/or T-cell epitopes.23. The baculoviral vector according to claim 17 , wherein said virus-like particle further comprises proteins forming a complete virus-like surface and optionally capsid and/or nucleopore proteins.24. The baculoviral vector according to claim 17 , wherein ...

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12-01-2017 дата публикации

PD1 AND PDL1 ANTIBODIES AND VACCINE COMBINATIONS AND USE OF SAME FOR IMMUNOTHERAPY

Номер: US20170007693A1
Принадлежит:

Disclosed herein is a vaccine comprising an antigen and PD1 antibody and/or PDL1 antibody. Also disclosed herein is a method for enhancing an immune response in a subject. The method may comprise administering the vaccine to the subject in need thereof. 1. A composition for enhancing an immune response against an antigen in a subject in need thereof , comprising:a) PD1 antibody or PDL1 antibody, or combination thereof, andb) a synthetic antigen capable of generating an immune response in the subject, or an immunogenic fragment or variant thereof.2. The composition of wherein the synthetic antigen is an isolated DNA that encodes for the antigen.3Plasmodium falciparumC. difficle.. The composition of wherein the synthetic antigen is selected from the group consisting of: hTERT claim 2 , prostate claim 2 , WT1 claim 2 , tyrosinase claim 2 , NYES01 claim 2 , PRAME claim 2 , MAGE claim 2 , CMV claim 2 , herpes claim 2 , HIV claim 2 , HPV claim 2 , HCV claim 2 , HBV claim 2 , influenza claim 2 , RSV claim 2 , claim 2 , and4. The composition of claim 3 , wherein the HPV antigen is E6 and E7 domains of subtypes selected from the group consisting of: HPV6 claim 3 , HPV11 claim 3 , HPV16 claim 3 , HPV18 claim 3 , HPV31 claim 3 , HPV33 claim 3 , HPV52 claim 3 , and HPV58 claim 3 , and a combination thereof.5. The composition of claim 3 , wherein the HIV antigen is selected from the group consisting of: Env A claim 3 , Env B claim 3 , Env C claim 3 , Env D claim 3 , B Nef-Rev claim 3 , and Gag claim 3 , and a combination thereof.6. The composition of claim 3 , wherein the influenza antigen is selected from the group consisting of: H1 HA claim 3 , H2 HA claim 3 , H3 HA claim 3 , H5 HA claim 3 , BHA antigen claim 3 , and any combination thereof.7Plasmodium falciparum. The composition of claim 3 , wherein the antigen includes a circumsporozoite (CS) antigen.8C. difficle. The composition of claim 3 , wherein the antigen is selected from the group consisting of: Toxin A claim 3 , and ...

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11-01-2018 дата публикации

LIPID A MIMICS, METHODS OF PREPARATION, AND USES THEREOF

Номер: US20180009833A1
Принадлежит: Immunovaccine Technologies Inc.

The invention provides lipid A mimics in which one or both of the sugar residues of a natural lipid A disaccharide backbone has been replaced with an aromatic group. These lipid A mimics may further differ from a natural lipid A molecule with respect to other structural characteristics, such as, a different number of phosphate groups present, changes in the number, structure and location of lipid chains and/or changes in the spacing and linkage of the sugar residues (or their aromatic replacements). The lipid A mimics may be lipid A agonists and as such may be useful as immunostimulatory agents in inducing or patenting an antibody and/or cell-mediated immune response, or may be lipid A antagonists and as such may be useful in treating or preventing a lipopolysaccharide (LPS)/lipid A-mediated disease or disorder. Also provided are methods for preparing the lipid A mimics. 24-. (canceled)7. (canceled)10. The compound of claim 8 , or pharmaceutically acceptable salt thereof claim 8 , wherein Xis —OP(O)(OH); Yis —NH—R; and Yis —O—R.14. The compound of claim 13 , or pharmaceutically acceptable salt thereof claim 13 , wherein Xis —OP(O)(OH); Yis —NH—R; Yis —O—R; and Yis —OH.16. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein D is —O—.17. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein at least one of A or Land at least one of E or Lindividually comprises one or more lipid chain substituents.26. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , which:has lipid A or lipopolysaccharide (LPS) antagonist activity;has immunostimulatory activity; and/oris capable of binding to toll-like receptor 4 (TLR4).27. (canceled)28. A pharmaceutical composition comprising the compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier claim 1 , diluent or excipient.29. (canceled)30. A vaccine composition comprising the ...

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14-01-2021 дата публикации

DETECTION OF NUCLEIC ACIDS FROM MULTIPLE TYPES OF HUMAN PAPILLOMAVIRUS

Номер: US20210010095A1
Принадлежит:

Nucleic acid oligonucleotide sequences are disclosed which include amplification oligomers and probe oligomers which are useful for detecting multiple types of human papillomaviruses (HPV) associated with cervical cancer. Methods for detecting multiple HPV types in biological specimens by amplifying HPV nucleic acid sequences in vitro and detecting the amplified products are disclosed. 1. A detection reaction mixture comprising:at least one detection probe comprising (a) a target-specific sequence selected from the group consisting of SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, complements thereof, and RNA equivalents thereof; and (b) a detectable label that is joined directly or indirectly to the target-specific sequence of (a).2. The detection reaction mixture of claim 1 , wherein the detection reaction mixture further comprises a lithium salt selected from the group consisting of lithium succinate and lithium chloride.3. The detection reaction mixture of claim 2 , wherein the reaction mixture comprises both lithium succinate and lithium chloride.4. The detection reaction mixture of claim 1 , wherein the detection reaction mixture further comprises lithium lauryl sulfate.5. The detection reaction mixture of claim 4 , wherein the detection reaction mixture further comprises a lithium salt selected from the group consisting of lithium succinate and lithium chloride.6. The detection reaction mixture of claim 1 , wherein the detectable label is a chemiluminescent compound.7. The detection reaction mixture of claim 6 , wherein the chemiluminescent compound is an acridinium ester (AE) compound.8. An aqueous formulation comprising:(a) at least one detection probe oligomer comprising (i) a target-specific sequence selected from the group consisting of SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, complements thereof, and RNA equivalents thereof, and (ii) a detectable label that is joined directly or indirectly to the target-specific sequence of (i);(b) a lithium salt selected ...

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09-01-2020 дата публикации

EFFICIENT CELL FREE PRODUCTION OF PAPILLOMAVIRUS GENE TRANSFER VECTORS

Номер: US20200010850A1
Принадлежит:

Methods of preparing papillomavirus nucleic acid transfer vectors, in-disassembled cluding by disassembly/reassembly of papillomavirus L1 and L2 virus-like particles, in a defined, cell-free high-efficiency production protocol. These methods may be used to efficiently encapsidate desired moieties, e.g., toxic or therapeutic nucleic acids such as DNA and RNA, and the resultant pseudovirus particles may be used as in vivo delivery vehicles. 113-. (canceled)14. A method of producing a papillomavirus pseudovirus comprising a therapeutic nucleic acid molecule , the method comprising:a. mixing a virus like particle (VLP) comprising papillomavirus L1 and L2 proteins, with the therapeutic nucleic acid molecule, wherein the mixture lacks cellular factors; and,b. incubating the mixture under conditions such that the VLP encapsidates the therapeutic nucleic acid molecule, thereby producing a papillomavirus pseudovirus comprising the therapeutic nucleic acid molecule.151. The method of claim , wherein the papillomavirus pseudovirus comprising the therapeutic nucleic acid molecule has an infectivity to particle ratio of at least 1×10i.u./mg L1 protein.161. The method of claim , wherein the mixture comprises less than 600 mM NaCl.171. The method of claim , wherein the pH of the mixture is in the range of from 5.2 to less than 8.2.181. The method of claim , wherein the step of mixing comprise contacting the VLP with at least 50 ng of the therapeutic nucleic acid molecule.191. The method of claim , wherein the L1 and L2 proteins are from a HPV type selected from the group consisting of α4 , α5 , α7 , α8 , α9 , α10 , β1 and β1.201. The method of claim , wherein prior to the step of incubating the mixture to encapsidate the therapeutic nucleic acid molecule , the VLP is disassembled.21. The method of claim 20 , wherein disassembly of the VLP comprises subjecting the VLP to conditions comprising less than 200 mM NaCl.22. The method of claim 21 , wherein disassembly comprises a ...

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21-01-2016 дата публикации

VACCINE COMBINATIONS

Номер: US20160015804A1
Принадлежит:

Vaccine combinations which comprise at least two or more of the following antigens: DTap-HEV-HepB-HPV suitable for administration in humans. A number of variations in the combination of these antigens have been disclosed that is suitable for concomitant administration. The methods of preparing the vaccine combinations are disclosed. Nucleic acids encoding the antigens, as well as methods for their production and use are provided.

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21-01-2016 дата публикации

Bispecific Molecules That are Immunoreactive with Immune Effector Cells That Express an Activating Receptor and an Antigen Expressed by a Cell Infected by a Virus and Uses Thereof

Номер: US20160017038A1
Автор: Scott Koenig
Принадлежит: Macrogenics Inc

The present invention relates to bispecific molecules that are capable of localizing an immune effector cell that expresses an activating receptor to a virally infected cell, so as to thereby facilitate the killing of the virally infected cell. In a preferred embodiment, such localization is accomplished using bispecific molecules that are immunoreactive with an activating receptor of an immune effector cell and to an antigen expressed by a cell infected with a virus wherein the antigen is detectably present on the cell infected with the virus at a level that is greater than the level at which the antigen is detected on the virus by the bispecific molecules, and to the use of such bispecific molecules in the treatment of latent viral infections.

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25-01-2018 дата публикации

USES OF HYDROXYBENZOPHENONE IN PREPARATION OF ANTIVIRAL AND ANTITUMOR DRUGS

Номер: US20180021269A1
Автор: JIANG GUANGYU, QIN WEIHUA
Принадлежит:

The present invention relates to uses of a benzophenone compound and analogues thereof having a symmetrical core structure and having same or different number of hydroxyl substitutions in benzene rings in the preparation of drugs for preventing and treating viral infections and anti-tumor drugs, in particular the use in the preparation of drugs for preventing and treating HIV, herpes virus and papillomavirus infection and the diseases induced thereby, wherein such viral infections include AIDS, genital warts, flat warts, common warts, herpes simplex, herpes zoster, vaginitis, cervicitis, cervical erosion and senile dementia, as well as cervical cancer, lung cancer, gastric cancer and colon cancer induced thereby, by means of preparing the hydroxy-substituted benzophenones and analogues thereof together with various compatible excipients into different medicaments or personal disinfected sanitary articles. 1. Use of a hydroxy-substituted benzophenone compound in the preparation of drugs for prevention and treatment of viral infections and anti-tumor drugs , wherein the hydroxy-substituted benzophenone compound is a compound selected from the group consisting of 2 ,3 ,4 ,2′ ,3′ ,4′-hexahydroxybenzophenone , 2 ,3 ,4 ,2′ ,4′ ,5-hexahydroxybenzophenone and 3 ,4 ,5 ,2′ ,3′ ,4′ ,-hexahydroxybenzophenone.2. The use according to claim 1 , wherein an effective amount of the compound and/or a composition containing the compound as an active ingredient are prepared together with various excipients for injections or oral preparations into power injections claim 1 , water injections claim 1 , infusions claim 1 , tablets claim 1 , capsules claim 1 , granules or solutions.3. The use according to claim 1 , an effective amount of the compound and/or a composition containing the compound as an active ingredient are prepared together with various compatible excipients for mucocutaneous preparations into pastes claim 1 , gels claim 1 , suppositories claim 1 , tablets claim 1 , lotions ...

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22-01-2015 дата публикации

Antibodies Against E7 Protein of Human Papilloma Virus (HPV)

Номер: US20150023979A1
Автор: Kuhne Christian
Принадлежит: VALDOSPAN GMBH

The invention discloses a method for preparing Human Papilloma Virus protein E7 antigen (HPV E7 antigen) comprising the following steps: —providing a purified preparation of HPV protein E7; —phosphorylating the HPV protein E7 in the preparation; —purifying the phosphorylated E7 protein with an anion exchange chromatography, wherein the phosphorylated E7 protein is separated from the non-phosphorylated E7 protein by a step wherein the non-phosphorylated E7 protein stays bound to an anion exchanger during the anion exchange chromatography whereas the phosphorylated E7 protein is obtained in the eluate of the anion exchange chromatography, thereby—obtaining a purified preparation of a phosphorylated HPV protein E7 antigen. The invention further discloses antibodies specific to this antigen, a kit and method for using such antibodies in clinical diagnostics and methods for generation of such antibodies. 115.-. (canceled)16. A method for preparing Human Papilloma Virus protein E7 antigen (HPV E7 antigen) comprising:providing a purified preparation of HPV protein E7;phosphorylating the HPV protein E7 in the preparation;purifying the phosphorylated E7 protein with an anion exchange chromatography, wherein the phosphorylated E7 protein is separated from the non-phosphorylated E7 protein by a step wherein the non-phosphorylated E7 protein stays bound to an anion exchanger during the anion exchange chromatography whereas the phosphorylated E7 protein is obtained in the eluate of the anion exchange chromatography; andobtaining a purified preparation of a phosphorylated HPV protein E7 antigen.17. The method of claim 16 , wherein phosphorylation is performed with a Casein Kinase (EC 2.7.11.1).18. The method of claim 17 , wherein phosphorylation is performed with Casein Kinase I or Casein Kinase II.19. The method of claim 18 , wherein the phosphorylation is performed with recombinant Casein Kinase II claim 18 , Casein Kinase II from rat liver claim 18 , or Casein Kinase II from ...

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22-01-2015 дата публикации

POLYNUCLEOTIDES FOR TREATING ONCOGENIC VIRAL POLYPEPTIDE POSITIVE TUMORS

Номер: US20150023996A1
Принадлежит:

This document relates to polynucleotides encoding antigenic polypeptides to induce an immune response to oncogenic viral polypeptides. Also provided are compositions comprising polynucleotides encoding antigenic polypeptides, and methods of use. In the provided methods, the virus can be a human papilloma virus. In some embodiments, a method for killing a cell expressing a first oncogenic viral polypeptide in a subject is provided. The method includes administering to the subject a composition in an amount sufficient to initiate an immune response against the first oncogenic viral peptide, where the composition comprises a pharmaceutically acceptable carrier and a polynucleotide provided herein and the immune response is effective to cause a cytotoxic effect in the cell. In some embodiments, the polynucleotide includes a second nucleotide sequence encoding a second antigenic polypeptide. The first oncogenic viral polypeptide can be E6 and the second oncogenic viral polypeptide can be E7. 1. An isolated polynucleotide comprising at least one nucleotide sequence encoding at least one antigenic polypeptide , wherein said at least one antigenic polypeptide:a. comprises an amino acid sequence having at least 70% sequence identity to the amino acid sequence of an oncogenic viral polypeptide, wherein said oncogenic viral polypeptide is selected from the group consisting of E6 and E7 of human papilloma virus;b. is capable of initiating an immune response to the oncogenic viral polypeptide in an immune-competent host; andc. is non-oncogenic in the immune-competent host.2. (canceled)3. (canceled)4. (canceled)5. The polynucleotide of claim 1 , wherein the at least one nucleotide sequence encodes SEQ ID NO:2 having a mutation selected from the group consisting of:a. a point mutation or deletion at L50;b. a point mutation or deletion at E148;c. a point mutation or deletion at T149;d. a point mutation or deletion at Q150; ande. a point mutation or deletion at L151.6. The ...

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24-01-2019 дата публикации

Oncolytic virus and checkpoint inhibitor combination therapy

Номер: US20190022203A1
Автор: Brian Lichty, John Bell
Принадлежит: MCMASTER UNIVERSITY, Turnstone Lp

The present invention pertains to a combination for simultaneous, separate or sequential use which comprises (a) an oncolytic virus and (b) a checkpoint inhibitor and to its use for the treatment of cancer.

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25-01-2018 дата публикации

NEISSERIA MENINGITIDIS COMPOSITIONS AND METHODS THEREOF

Номер: US20180022783A1
Принадлежит:

In one aspect, the invention relates to a composition including a first polypeptide having the sequence set forth in SEQ ID NO: 1 and a second polypeptide having the sequence set forth in SEQ ID NO: 2. In one embodiment, the composition includes about 120 μg/ml of a first polypeptide including the amino acid sequence set forth in SEQ ID NO: 1, 120 μg/ml of a second polypeptide including the amino acid sequence set forth in SEQ ID NO: 2, about 2.8 molar ratio polysorbate-80 to the first polypeptide, about 2.8 molar ratio polysorbate-80 to the second polypeptide, about 0.5 mg/ml aluminum, about 10 mM histidine, and about 150 mM sodium chloride. In one embodiment, a dose of the composition is about 0.5 ml in total volume. In one embodiment, two-doses of the composition induce a bactericidal titer against diverse heterologous subfamily A and subfamily B strains in a human. 1. A composition comprisinga) a first lipidated polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 1, andb) a second lipidated polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 2.2. The composition according to claim 1 , further comprising polysorbate-80 claim 1 , aluminum claim 1 , histidine claim 1 , and sodium chloride.3. The composition according to claim 2 , wherein the composition comprises about 120 μg/ml of the first polypeptide; about 120 μg/ml of the second polypeptide; about 2.8 molar ratio of polysorbate-80; about 0.5 mg/ml aluminum; about 10 mM histidine;and about 150 mM sodium chloride.4. The composition according to claim 2 , wherein the composition comprises about 60 μg of the first polypeptide; about 60 μg of the second polypeptide; about 18 μg polysorbate-80; about 250 μg aluminum; about 780 μg histidine; and about 4380 μg sodium chloride claim 2 , per 0.5 ml dose.5. The composition according to claim 1 , wherein the composition induces a bactericidal titer of serum immunoglobulin that is at least greater than 1-fold higher in a human after ...

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28-01-2021 дата публикации

HUMAN PAPILLOMAVIRUS VACCINES AND USES OF THE SAME

Номер: US20210024586A1
Принадлежит:

Provided herein are engineered human papilloma virus (HPV) molecular vaccine constructs. Vaccine constructs can also include ligand-inducible engineered gene switch systems for modulating expression of heterologous genes, such as a cytokines, in host cells. 1. A non-naturally occurring polynucleotide encoding a polypeptide comprising one or more immune response-inducing human papilloma virus (HPV) polypeptides.2. The polynucleotide of claim 1 , wherein said non-naturally occurring polynucleotide encodes a polypeptide comprising two or more HPV polypeptides.3. The polynucleotide of claim 2 , wherein said two or more HPV polypeptides comprise:(i) at least one HPV-16 peptide;(ii) at least one HPV-18 peptide; or(iii) both (i) and (ii).4. The polynucleotide of claim 3 , wherein:(i) said HPV-16 peptide comprises at least one of an E5 peptide, an E6 peptide or an E7 peptide;(ii) said HPV-18 peptide comprises at least one of an E5 peptide, an E6 peptide or an E7 peptide; or(iii) both (i) and (ii).5. The polynucleotide of or claim 3 , wherein(i) said HPV-16 peptide comprises an E5 peptide, and said E5 peptide has a sequence as shown in SEQ ID NO: 47;(ii) said HPV-16 peptide comprises an E6 peptide, and said E6 peptide has a sequence as shown in SEQ ID NO: 45;(iii) said HPV-16 peptide comprises an E7 peptide, and said E7 peptide has a sequence as shown in SEQ ID NO: 46;(iv) said HPV-18 peptide comprises an E5 peptide, and said E5 peptide has a sequence as shown in SEQ ID NO: 50;(v) said HPV-18 peptide comprises an E6 peptide, and said E6 peptide has a sequence as shown in SEQ ID NO: 48;(vi) said HPV-18 peptide comprises an E7 peptide, and said E7 peptide has a sequence as shown in SEQ ID NO: 49; or(vii) any combination thereof.6. The polynucleotide of any one of to claim 3 , wherein said polypeptide has a sequence as shown in SEQ ID NO: 51.7. The polynucleotide of any one of to claim 3 , wherein at least one of said one or more HPV polypeptides is connected to an agonist ...

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29-01-2015 дата публикации

BACULOVIRUS-BASED VACCINES

Номер: US20150030621A1
Принадлежит:

The present invention relates to a recombinant baculovirus comprising: (a) a nucleotide sequence encoding a foreign virus envelope protein; (b) a first promoter operatively linked to the envelope-encoding nucleotide sequence; (c) a nucleotide sequence encoding an antigen protein; and (d) a second promoter operatively linked to the antigen-encoding nucleotide sequence; and a vaccine composition using the same. The recombinant baculovirus of the present invention has an excellent efficacy on both humoral and cellular immune responses against a specific antigen (e.g., HPV L1), enabling to function as a more efficient DNA vaccine. 119-. (canceled)20. A method for inducing an immune response against a specific antigen in a mammalian subject in need thereof , comprising:(a) transfecting into a insect cell a recombinant bacmid comprising: (i) a nucleotide sequence encoding an envelope protein of an endogenous retrovirus; (ii) a first promoter that is operable in insect cells and is operatively linked to (i); (iii) a nucleotide sequence encoding an antigen protein; and (iv) a second promoter that is derived from a mammalian genome or virus and is operatively linked to (iii);(b) obtaining a recombinant baculovirus which is produced from the insect cell; and(c) administering a pharmaceutically effective amount of the recombinant baculovirus of (b) to the mammalian subject.21. The method according to claim 20 , wherein the antigen comprises a viral antigen claim 20 , a bacterial antigen claim 20 , a parasitic antigen or a cancer antigen.22. The method according to claim 21 , wherein the antigen comprises the viral antigen selected from the group consisting of HPV (human papillomavirus) antigen claim 21 , HBV (hepatitis B virus) antigen claim 21 , HCV (hepatitis C virus) antigen claim 21 , HIV (human immunodeficiency virus) antigen claim 21 , rotavirus antigen claim 21 , influenza virus antigen claim 21 , HSV (herpes simplex virus) antigen claim 21 , avian influenza virus ...

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31-01-2019 дата публикации

RECOMBINANT LISTERIA VACCINE STRAINS AND METHODS OF USING THE SAME IN CANCER IMMUNOTHERAPY

Номер: US20190030145A1
Автор: Paterson Yvonne

The present invention provides methods of treating, protecting against, and inducing an immune response against a human papillomavirus-associated oropharyngeal tumor or cancer, comprising the step of administering to a subject a recombinant strain expressing a human papillomavirus antigen. 1ListeriaListeria. A method of inducing an anti-tumor or an anti-cancer immune response in a human subject having a tumor or cancer , the method comprising the step of administering to said subject a composition comprising a recombinant strain comprising a recombinant nucleic acid , said nucleic acid comprising a first open reading frame encoding a recombinant polypeptide comprising an N-terminal fragment of a listeriolysin O (LLO) protein fused to a heterologous antigen or fragment thereof , wherein said LLO protein comprises a sequence selected from SEQ ID NO: 2 , SEQ ID NO: 4 , AA 20-442 of SEQ ID NO: 1 , or AA 1-420 of SEQ ID NO: 1 , wherein said recombinant nucleic acid further comprises a second open reading frame encoding a mutant prfA gene or a metabolic enzyme , wherein said comprises a gene deletion or mutation , thereby inducing an immune response against a tumor or a cancer , wherein said tumor or cancer is a head and neck tumor or cancer , wherein said method further comprises administering a radiation or chemotherapeutic treatment in said subject , and wherein said immune response comprises reducing the severity of side effects associated with said a radiation or chemotherapeutic treatment in said subject.2. The method of claim 1 , wherein said head and neck tumor or cancer is an oropharyngeal tumor or cancer.3. The method of claim 1 , wherein said administering is intravenous administering.4Listeria. The method of claim 1 , wherein said recombinant strain is administered to said human subject at a dose of 1×10-3.31×10organisms.5ListeriaListeria monocytogenes. The method of claim 1 , wherein said recombinant strain is a recombinant strain.6Listeria. The method of ...

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31-01-2019 дата публикации

PAPILLOMAVIRUS CHIMERIC PROTEIN AND APPLICATION THEREOF

Номер: US20190031724A1
Принадлежит:

Provided is a papillomavirus chimeric protein, the skeleton thereof being a papillomavirus L1 protein or a mutant thereof, at least one human papillomavirus 33-type L2 protein or mutant polypeptide thereof being embedded on the skeleton. The present papillomavirus chimeric protein can be used for preparing a vaccine for preventing papillomavirus infections and infection induced disease. 1. A chimeric papillomavirus protein comprising papillomavirus L1 protein or a mutant of papillomavirus L1 protein as scaffold , characterized in that , at least one polypeptide derived from HPV33 L2 protein or from a mutant of HPV33 L2 protein is inserted into said scaffold.2. The chimeric papillomavirus protein according to claim 1 , characterized in that claim 1 , said polypeptide is derived from any fragment of the consecutive 8-33 amino acids within aa. 1-200 of the HPV33 L2 protein claim 1 , preferably claim 1 , the amino acid sequence of said polypeptide is shown as SEQ ID No.1; or claim 1 , said polypeptide is a polypeptide obtained by extending or truncating 1-5 amino acids from the sequence shown as SEQ ID No.1 at N-terminus and/or C-terminus; preferably claim 1 , the amino acid sequence of said polypeptide is shown as SEQ ID No. 2 or SEQ ID No.3.3. The chimeric papillomavirus protein according to claim 1 , characterized in that claim 1 , the scaffold is HPV16 L1 protein or a mutant of the HPV16 L1 protein; preferably claim 1 , the mutant of the HPV16 L1 protein is obtained by truncating 0-9 amino acids at the N-terminus and/or 0-34 amino acids at the C-terminus from the HPV16 L1 protein; more preferably claim 1 , the amino acid sequence of the scaffold is shown as SEQ ID No.4 or the amino acid sequence of SEQ ID No.4 with 31 amino acid deletion at the C-terminus.4. The chimeric papillomavirus protein according to claim 3 , characterized in that claim 3 , the HPV33 L2 protein-derived polypeptide is inserted into the surface region of the HPV16 L1 protein or of the mutant of ...

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30-01-2020 дата публикации

Detection of nucleic acids from multiple types of human papillomavirus

Номер: US20200032355A1
Принадлежит: Gen Probe Inc

Nucleic acid oligonucleotide sequences are disclosed which include amplification oligomers and probe oligomers which are useful for detecting multiple types of human papillomaviruses (HPV) associated with cervical cancer. Methods for detecting multiple HPV types in biological specimens by amplifying HPV nucleic acid sequences in vitro and detecting the amplified products are disclosed.

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12-02-2015 дата публикации

CORRELATION OF DISEASE ACTIVITY WITH CLONAL EXPANSIONS OF HUMAN PAPILLOMAVIRUS 16-SPECIFIC CD8+ T-CELLS IN PATIENTS WITH SEVERE EROSIVE ORAL LICHEN PLANUS

Номер: US20150044252A1
Принадлежит:

A massive clonal expansion of activated CD8 T-cells with increased frequency of HPV 16-specific CD8 T-cells was discovered to be a characteristic of oral lichen planus (OLP), indicating a causal link between HPV infection and the dysimmune process. The invention relates to compositions and methods for the diagnosis and treatment of OLP patients. 1. A method for monitoring treatment of an oral lichen planus patient comprising:providing a cell sample from an oral lichen planus patient;detecting the presence of a human papilloma virus or an immune response against a human papilloma virus infection in the cell sample;treating the patient with an anti-HPV treatment; anddetecting a reduction in an oral lichen planus symptom.2. The method of claim 1 , wherein the cell sample is a lesion from an oral lichen planus patient.3. The method of claim 1 , wherein the cell sample is a blood sample from an oral lichen planus patient.4. The method of claim 2 , wherein the presence of an immune response against a human papilloma virus infection is detected.5. The method of claim 3 , wherein the presence of an immune response against a human papilloma virus infection is detected.6. The method of claim 3 , wherein the presence of a human papilloma virus is detected.7. The method of claim 6 , wherein the human papilloma virus is of a type selected from types 16 claim 6 , 18 claim 6 , 31 claim 6 , 33 claim 6 , 35 claim 6 , 39 claim 6 , 45 claim 6 , 51 claim 6 , 52 claim 6 , 56 claim 6 , 58 claim 6 , 59 claim 6 , 68 claim 6 , 69 claim 6 , 73 claim 6 , and 82.8. (canceled)9Bordetella. The method of claim 1 , wherein the anti-HPV treatment is selected from a composition comprising the major capsid protein L1 of HPV types 6 claim 1 , 11 claim 1 , 16 claim 1 , and 18; a composition comprising the major capsid protein L1 of HPV types 16 claim 1 , and 18; and at least one chimeric recombinant sp. adenylate cyclase (CyaA) protein or fragment thereof claim 1 , the CyaA protein or fragment thereof ...

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16-02-2017 дата публикации

RECOMBINANT LISTERIA VACCINE STRAINS AND METHODS OF PRODUCING THE SAME

Номер: US20170042996A1
Автор: Petit Robert, WALLECHA Anu
Принадлежит:

The present invention provides methods of treating, protecting against and inducing an immune response against a tumor or cancer, comprising the step of administering to a subject a recombinant strain. In one embodiment the present invention relates to a recombinant strain, said recombinant strain comprising a recombinant nucleic add, said nucleic add comprising a first open reading frame encoding a recombinant polypeptide comprising a first N-terminal fragment of an LLO protein fused to a heterologous antigen or fragment thereof, and wherein said recombinant nucleic add further comprises a second open reading frame encoding a mutant PrfA protein. 1ListeriaListeria. A recombinant strain , said recombinant strain comprising a recombinant nucleic acid , said nucleic acid comprising a first open reading frame encoding a recombinant polypeptide comprising an N-terminal fragment of an LLO protein fused to a heterologous antigen or fragment thereof , and wherein said recombinant nucleic acid further comprises a second open reading frame encoding a mutant PrfA protein.2ListeriaListeria. The recombinant of claim 1 , wherein said comprises a deletion claim 1 , inactivation or mutation in the prfA gene.3Listeria. The recombinant of any one of - claim 1 , wherein said mutant PrfA protein comprises a D133V mutation.4ListeriaListeriaListeria. The recombinant of any one of - claim 1 , wherein said mutant PrfA protein encoded by said second open reading frame complements said prfA genomic mutation claim 1 , deletion or inactivation in said strain or restores partial PrfA function in said strain.5Listeria. The recombinant of any one of - claim 1 , wherein said heterologous antigen is Human Papilloma Virus-E7 (HPV-E7) or HPV-E6.6Listeria. The recombinant strain of any one of - claim 1 , wherein said N-terminal fragment of an LLO protein is selected from a sequence comprising SEQ ID NO: 2 or SEQ ID NO: 4.7ListeriaListeriaListeria monocytogenes. The recombinant strain of any one of - ...

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25-02-2021 дата публикации

HETEROLOGOUS COMBINATION PRIME:BOOST THERAPY AND METHODS OF TREATMENT

Номер: US20210052712A1
Автор: STOJDL DAVID F.

The present disclosure provides a Farmington virus formulated to induce an immune response in a mammal against a tumour associated antigen. The Farmington virus may express an antigenic protein that includes an epitope from the tumour associated antigen. The Farmington virus may be formulated in a composition where the virus is separate from an antigenic protein that includes an epitope from the tumour associated antigen. The present disclosure also provides a prime:boost therapy for use in inducing an immune response in a mammal. The boost includes a Farmington virus, or a composition that includes a Farmington virus. 1. A Farmington virus comprising a nucleic acid that is capable of expressing a tumour associated antigen or an epitope thereof.2. The Farmington virus of claim 1 , wherein the genomic backbone of the Farmington virus encodes a protein having at least 90% sequence identity with any one of SEQ ID NOs 3-7.3. The Farmington virus of claim 2 , wherein the genomic backbone of the Farmington virus encodes a protein having at least 95% sequence identity with any one of SEQ ID NOs 3-7.4. The Farmington virus of any one of - claim 2 , wherein the tumour associated antigen is a foreign antigen.5. The Farmington virus of claim 4 , wherein the foreign antigen comprises E6 protein from HPV or E7 protein from HPV.6. The Farmington virus of claim any one of - claim 4 , wherein the tumour associated antigen is a self antigen.7. The Farmington virus of claim 6 , wherein the self antigen is MAGEA3.8. The Farmington virus of claim any one of - claim 6 , wherein the tumour associated antigen is a neoepitope.9. The Farmington virus of any one of - claim 6 , wherein the Farmington virus induces an immune response against the tumour associated antigen in a mammal to whom the Farmington virus is administered.10. The Farmington virus of claim 9 , wherein the mammal has been previously administered a prime that is immunologically distinct from the Farmington virus.11. The ...

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22-02-2018 дата публикации

METHOD

Номер: US20180050105A1
Автор: Hogset Anders
Принадлежит: PCI BIOTECH AS

The invention concerns a method of generating an immune response in a subject, comprising administering to the subject an antigenic molecule, a photosensitizing agent, a checkpoint inhibitor, and irradiating said subject with light of a wavelength effective to activate the photosensitizing agent to generate an immune response. Preferably the method is a method of vaccination. The invention also provides related methods, compositions, cells, uses, products and kits. 1. A method of generating an immune response in a subject , comprising administering to said subject an antigenic molecule , a photosensitizing agent , a checkpoint inhibitor , and irradiating said subject with light of a wavelength effective to activate said photosensitizing agent , wherein an immune response is generated.2. A method as claimed in wherein the checkpoint inhibitor is an antibody claim 1 , preferably a monoclonal antibody.3. A method as claimed in or wherein the checkpoint inhibitor is selected from anti-CTLA4 and anti-PD-1 claim 1 , preferably (i) anti-CTLA4 and anti-PD-1 or (ii) anti-CTLA4.4. A method as claimed in any one of to wherein the method further comprises contacting said subject with a TLR ligand.5. A method as claimed in wherein said TLR ligand is a TLR3 ligand claim 4 , preferably a double stranded RNA molecule claim 4 , preferably Poly(I:C).6. The method as claimed in any one of to wherein the antigenic molecule is a molecule capable of stimulating an immune response claim 4 , preferably a vaccine antigen or vaccine component and preferably comprises more than one antigen.7. The method as claimed in any one of to wherein the photosensitising agent is selected from TPCS claim 4 , AlPcS claim 4 , TPPSand TPBS claim 4 , preferably TPCS.8. The method as claimed in any one of to wherein the antigenic molecule is a peptide claim 4 , preferably a melanoma peptide or Human Papillomavirus (HPV) peptide.9. The method as claimed in any one of to wherein said method is a method of ...

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23-02-2017 дата публикации

THERAPEUTIC HPV18 VACCINES

Номер: US20170051019A1
Принадлежит:

Provided is designer nucleic acid constructs and polypeptides that can be used as therapeutic vaccines against HPV18 and/or HPV16. 1. A nucleic acid molecule encoding a first polypeptide comprising SEQ ID NO: 20.2. The nucleic acid molecule of claim 1 , wherein the first polypeptide further comprises at least one epitope of a human papillomavirus (HPV) E2 protein.3. The nucleic acid molecule of claim 2 , wherein the first polypeptide comprises HPV18 E2 protein having a deletion or mutation in its DNA binding domain and/or a mutation in its transactivation domain.4. The nucleic acid molecule of claim 3 , wherein the first polypeptide comprises SEQ ID NO: 22.5. The nucleic acid molecule of claim 1 , comprising SEQ ID NO: 21.6. The nucleic acid molecule of claim 1 , comprising SEQ ID NO: 23.7. A vector comprising the nucleic acid molecule of claim 1 , wherein nucleic acid encoding the first polypeptide is operably linked to a promoter.8. The vector of claim 7 , wherein the vector is a recombinant adenovirus.9. The vector of claim 7 , wherein the promoter is operably coupled to a repressor operator sequence claim 7 , to which a repressor protein can bind in order to repress expression of the promoter in the presence of the repressor protein.10. The vector of claim 7 , further comprising:nucleic acid encoding a second polypeptide operably linked to a promoter, wherein the second polypeptide comprises SEQ ID NO: 1.11. The vector of claim 10 , wherein the second polypeptide comprises SEQ ID NO: 3 or SEQ ID NO: 5.12. The vector of claim 11 ,wherein the first polypeptide comprises SEQ ID NO: 22, andwherein the second polypeptide comprises SEQ ID NO: 3.13. A vaccine composition comprising:{'claim-ref': {'@idref': 'CLM-00007', 'claim 7'}, 'the vector of , and'}a pharmaceutically acceptable excipient.14. A vaccine composition comprising:{'claim-ref': {'@idref': 'CLM-00007', 'claim 7'}, 'the vector of ;'}a second vector comprising a nucleic acid molecule encoding a second ...

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26-02-2015 дата публикации

HPV EPITOPES TARGETED BY T CELLS INFILTRATING CERVICAL MALIGNANCIES FOR USE IN VACCINES

Номер: US20150056234A1

The present invention relates to novel CD4+ and CD8+ T cell epitopes that are specific for HPV-specific E6 and E7 oncoproteins, to peptides comprising these novel T cell epitopes, and to (vaccine) compositions comprising these peptides for use in methods for the prevention and/or treatment of HPV related diseases. Preferred epitopes are recognized by a T cell that infiltrates a cervical neoplastic lesion or by a T cell from a draining lymph node, and are presented by an HLA-DQ or HLA-DP molecule, or an HLA-B. 1. A method for the prevention and/or treatment of an HPV related disease , wherein the method comprises the administration of an effective amount of a peptide-having a length of no more than 100 , 98 , 96 , 94 or 92 amino acids and comprising at least 19 contiguous amino acids from the amino acid sequence of at least one of an HPV E6 and E7 protein , wherein the contiguous amino acid sequence comprises an epitope that is presented by at least one of an HLA-DQ and HLA-DP molecule and wherein the epitope is not the epitope presented in the context of HLA-DQ2 and consisting of amino acid 35-50 of the HPV16 E7 protein.2. The method according to claim 1 , and wherein the contiguous amino acid sequence comprises an epitope that is recognized by a T cell that infiltrates a cervical neoplastic lesion or by a T cell from a draining lymph node.3. The method according to claim 1 , wherein the epitope is an epitope of an HPV E6 protein.4. The method according to claim 1 , wherein the epitope is an epitope of an HPV serotype 16 claim 1 , 18 claim 1 , 31 claim 1 , 33 or 45.5. The method according to claim 1 , wherein the epitope is selected from the group consisting of SEQ ID No.'s 6 claim 1 , 5 claim 1 , 7 claim 1 , 9 claim 1 , 10 claim 1 , 11 claim 1 , 12 claim 1 , 13 claim 1 , 16 claim 1 , 18 claim 1 , 19 claim 1 , 20 and 21.6. The method according to claim 1 , wherein the length of the contiguous amino acid sequence is 19-45 amino acids.7. The method according to claim ...

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28-02-2019 дата публикации

Mutant of L1 Protein of Human Papillomavirus Type 11

Номер: US20190062379A1
Принадлежит:

Disclosed are a mutated HPV11 L1 protein (or a variant thereof), a sequence encoding the same, a method for preparing the same, and a virus-like particle comprising the same, wherein the protein (or a variant thereof) and the virus-like particle can induce the generation of neutralizing antibodies against at least two HPV types (e.g. HPV11 and HPV6), and therefore can be used to prevent infection by said at least two HPV types, and a disease caused by said infection, such as cervical cancer and condyloma acuminatum. Also disclosed is use of the protein and the virus-like particle in the manufacture of a pharmaceutical composition or a vaccine for preventing infection by said at least two HPV types, and a disease caused by said infection, such as cervical cancer and condyloma acuminatum. 1. A mutated HPV11 L1 protein or a variant thereof , wherein as compared with a wild type HPV11 L1 protein , the mutated HPV11 L1 protein has the following mutations:(1) N-terminal truncation of 3, 4, 5 or 6 amino acids; and(2)(a) substitution of amino acid residues at positions 346-351 of the wild type HPV11 L1 protein with amino acid residues at the corresponding positions of a L1 protein of a wild-type HPV6; or(b) substitution of amino acid residues at positions 119-140 of the wild type HPV11 L1 protein with amino acid residues at the corresponding positions of a L1 protein of a wild type HPV6;and, the variant differs from the mutated HPV11 L1 protein only by substitution, addition or deletion of 1, 2, 3, 4, 5, 6, 7, 8 or 9) amino acids, and retains the function of the mutated HPV11 L1 protein, i.e. capability of inducing generation of neutralizing antibodies against HPV11 and HPV6.2. An isolated nucleic acid claim 1 , encoding the mutated HPV11 L1 protein or a variant thereof according to .3. A vector comprising the isolated nucleic acid according to .4. A host cell comprising the isolated nucleic acid according to and/or a vector comprising the isolate nucleic acid.5. A HPV ...

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27-02-2020 дата публикации

COMBINATION OF LISTERIA-BASED VACCINE WITH ANTI-CTLA-4 OR ANTI-CD137 ANTIBODIES

Номер: US20200061167A1
Принадлежит: ADVAXIS, INC.

The subject matter described herein is directed to methods of treating, protecting against, and inducing an immune response against a human papillomavirus-associated tumor or cancer, comprising the step of administering to a subject a recombinant strain expressing a construct comprising at least one human papillomavirus antigen in combination with one or more other therapeutic agents to treat a tumor or metastatic cancer. 1Listeria. A method of promoting an antigen-specific memory T-cell population comprising , administering to a subject an effective amount of a combination comprising , i. an immunogenic composition comprising a recombinant strain comprising a nucleic acid molecule , the nucleic acid molecule comprising a first open reading frame encoding a fusion polypeptide , wherein the fusion polypeptide comprises a truncated listeriolysin O (tLLO) protein , a truncated ActA protein , or a PEST amino acid sequence fused to a heterologous antigen or fragment thereof , and ii. an effective amount of a composition comprising an anti-CD137 antibody or a functional fragment thereof.2Listeria. A method for preventing reoccurrence of a tumor in a subject in need thereof , the method comprising administering to the subject an effective amount of a combination comprising , i. a immunogenic composition comprising a recombinant strain comprising a nucleic acid molecule , the nucleic acid molecule comprising a first open reading frame encoding a fusion polypeptide , wherein the fusion polypeptide comprises a truncated listeriolysin O (tLLO) protein , a truncated ActA protein , or a PEST amino acid sequence fused to a heterologous antigen or fragment thereof , and ii. an effective amount of a composition comprising an anti-CD137 antibody or a functional fragment thereof.3Listeria. A method for generating a durable antitumor T cell response in a subject in need thereof , the method comprising administering to the subject an effective amount of a combination comprising , i. an ...

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08-03-2018 дата публикации

LISTERIA-BASED IMMUNOGENIC COMPOSITIONS FOR ELICITING ANTI-TUMOR RESPONSES

Номер: US20180064765A1
Принадлежит:

The present invention is directed to compositions comprising an immune checkpoint inhibitor or a T cell stimulator or a combination thereof, and a live attenuated recombinant strain comprising a fusion polypeptide comprising a truncated Listeriolysin O protein, a truncated ActA protein, or a PEST amino acid sequence fused to a tumor-associated antigen. The invention is further directed to methods of treating, protecting against, and inducing an immune response against a tumor or a cancer, comprising the step of administering the same. 1Listeria. An immunogenic composition comprising (i) an immune checkpoint inhibitor and/or a T-cell stimulator , and (ii) a recombinant attenuated strain comprising a nucleic acid molecule , said nucleic acid molecule comprising a first open reading frame encoding a fusion polypeptide , wherein said fusion polypeptide comprises a truncated Listeriolysin O protein , a truncated ActA protein , or a PEST amino acid sequence fused to a heterologous antigen or fragment thereof.2. (canceled)3. (canceled)4Listeria. The composition of claim 1 , wherein said nucleic acid molecule is integrated into the genome.5Listeria. The composition of claim 1 , wherein said nucleic acid molecule is in a bacterial artificial chromosome in said recombinant strain.6Listeria. The composition of claim 1 , wherein said nucleic acid molecule is in a plasmid in said recombinant strain.7Listeria. The composition of claim 6 , wherein said plasmid is stably maintained in said recombinant strain in the absence of antibiotic selection.8Listeria.. The composition of claim 6 , wherein said plasmid does not confer antibiotic resistance upon said recombinant9. The composition of claim 1 , wherein said heterologous antigen is a tumor-associated antigen.10. The composition of claim 9 , wherein said tumor-associated antigen is a human papilloma virus (HPV).11. The composition of claim 9 , wherein said tumor-associated antigen is an angiogenic antigen.12. (canceled)13. ( ...

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09-03-2017 дата публикации

METHODS AND COMPOSITIONS FOR PRODUCING AN ADENOVIRUS VECTOR FOR USE WITH MULTIPLE VACCINATIONS

Номер: US20170065706A1
Принадлежит:

Methods for generating immune responses using adenovirus vectors that allow multiple vaccinations with the same adenovirus vector and vaccinations in individuals with preexisting immunity to adenovirus are provided. 136-. (canceled)37. A composition comprising a replication defective adenovirus vector comprising:a deletion in the E2b region; anda nucleic acid sequence encoding HPV E6, HPV E7 or a combination thereof.38. The composition of claim 37 , further comprising a replication defective adenovirus vector comprising a nucleic acid sequence encoding a tumor protein claim 37 , a viral coat protein claim 37 , a bacterial surface protein claim 37 , or a combination thereof.39. The composition of claim 37 , wherein the replication defective adenovirus vector further comprises a deletion in the E1 region claim 37 , a deletion in the E3 region claim 37 , a deletion in the E4 region claim 37 , or a combination thereof.40. The composition of claim 37 , wherein the replication defective adenovirus vector is not a gutted vector.41. The composition of claim 37 , wherein the composition comprises the replication defective adenovirus vector at a concentration of at least 10virus particles/ml.42. The composition of claim 37 , wherein the composition comprises the replication defective adenovirus vector at a concentration of at least 10virus particles/ml.43. The composition of claim 37 , wherein the composition comprises the replication defective adenovirus vector at a concentration of at least 10virus particles/ml.44. The composition of claim 37 , wherein the composition comprises the replication defective adenovirus vector at a concentration of at least 10virus particles/ml.45. The composition of claim 37 , wherein the composition comprises the replication defective adenovirus vector at a concentration of at least 10virus particles/ml.46. The composition of claim 37 , wherein the composition comprises the replication defective adenovirus vector at a concentration of at least ...

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09-03-2017 дата публикации

COMPOSITIONS, METHODS AND USES FOR THERMALLY STABLE HUMAN PAPILLOMAVIRUS FORMULATIONS

Номер: US20170065707A1
Принадлежит:

Embodiments of the present invention provide for novel compositions and methods for making and using a thermally stable human papilloma virus (HPV) formulation or other stabilized multimeric virus formulation. Certain embodiments concern lyophilizing HPV formulations in the presence or absence of adjuvants. Other embodiments concern lypophilizing HPV capsomere vaccines in order to increase stability of an immunogenic composition against HPV infection for storage, delivery and use. In yet other embodiments, a single immunogenic composition can include a thermally stable formulation of multiple virus serotypes. 1. An immunogenic composition comprising:a multimeric viral protein complex, wherein at least one viral protein of the multimeric viral protein complex is from a pathogenic virus;a glass-forming agent; andan adjuvant,wherein the immunogenic composition is essentially dried.2. The immunogenic composition according to claim 1 , wherein the adjuvant comprises a particulate adjuvant.3. The immunogenic composition according to claim 1 , further comprising a buffer comprising one or more volatile salts.4. The immunogenic composition according to claim 1 , further comprising at least one co-immunostimulatory agent selected from the group consisting of Glycopyranoside lipid A (GLA) claim 1 , lipid A claim 1 , lipid A derivatives claim 1 , monophosphoryl lipid A claim 1 , chemical analogues of monophosphoryl Lipid A claim 1 , CpG containing oligonucleotides claim 1 , TLR-4 agonists claim 1 , flagellin claim 1 , flagellins derived from gram negative bacteria claim 1 , TLR-5 agonists claim 1 , fragments of flagellins capable of binding to TLR-5 receptors claim 1 , saponins claim 1 , analogues of saponins claim 1 , QS-21 claim 1 , purified saponin fractions claim 1 , ISCOMS and saponin combinations with sterols and lipids claim 1 , or a combination thereof.5. (canceled)6. The immunogenic composition according to claim 4 , wherein the essentially dried immunogenic ...

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09-03-2017 дата публикации

Truncated L1 Protein of Human Papillomavirus Type 11

Номер: US20170065708A1
Принадлежит:

The invention relates to a truncated L1 protein of the Human Papillomavirus Type 11, a virus-like particle consisting of the protein, a vaccine comprising said virus-like particle, and the use of the vaccine in the prevention of condyloma acuminatum or HPV infections. 1. (canceled)2. (canceled)3. (canceled)4. (canceled)5. (canceled)6. (canceled)7. (canceled)8. (canceled)9. (canceled)10. (canceled)11. (canceled)12. (canceled)13. (canceled)14. A N-terminally truncated HPV11 L1 protein lacking exactly the first 4 amino acids at the N-terminal as compared to wild-type HPV11 L1 protein.15. The N-terminally truncated protein according to claim 14 , represented by a sequence set forth in SEQ ID NO.: 1.16. A polynucleotide encoding the N-terminally truncated protein according to .17. A vector that in terms of the HPV L1 protein only comprises the genetic information of the polynucleotide according to .18. A cell comprising the vector according to .19. A composition comprising the N-terminally truncated protein according to .20. A HPV 11 virus-like particle (VLP) comprising or consisting of the N-terminally truncated protein according to .21. A method for producing the N-terminally truncated HPV11 L1 protein according to claim 14 , comprising:{'i': 'E. coli', 'a) expressing a HPV L1 gene encoding the N-terminally truncated HPV L1 protein in an expression system;'}{'i': 'E. coli', 'b) disrupting the , which has expressed the N-terminally truncated HPV L1 protein, in a solution at a salt concentration of from 100 mM to 600 mM, and isolating the supernatant;'}c) decreasing the salt concentration of the supernatant of b) to from 100 mM to 0, inclusive, by using water or a low salt solution, and collecting a precipitate; andd) redissolving the precipitation of c) in a solution at a salt concentration of from 150 mM to 2500 mM, adding a reductant to it, and then isolating the resultant solution, wherein the solution contains the N-terminally truncated HPV L1 protein with a purity ...

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12-03-2015 дата публикации

NEISSERIA MENINGITIDIS COMPOSITIONS AND METHODS THEREOF

Номер: US20150071959A1
Принадлежит:

In one aspect, the invention relates to a composition including a first polypeptide having the sequence set forth in SEQ ID NO: 1 and a second polypeptide having the sequence set forth in SEQ ID NO: 2. In one embodiment, the composition includes about 120 μg/ml of a first polypeptide including the amino acid sequence set forth in SEQ ID NO: 1, 120 μg/ml of a second polypeptide including the amino acid sequence set forth in SEQ ID NO: 2, about 2.8 molar ratio polysorbate-80 to the first polypeptide, about 2.8 molar ratio polysorbate-80 to the second polypeptide, about 0.5 mg/ml aluminum, about 10 mM histidine, and about 150 mM sodium chloride. In one embodiment, a dose of the composition is about 0.5 ml in total volume. In one embodiment, two-doses of the composition induce a bactericidal titer against diverse heterologous subfamily A and subfamily B strains in a human. 1. A composition comprisinga) a first lipidated polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 1,b) a second lipidated polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 2,2. The composition according to claim 1 , further comprising polysorbate-80 claim 1 , aluminum claim 1 , histidine claim 1 , and sodium chloride.3. The composition according to claim 2 , wherein the composition comprises about 120 μg/ml of the first polypeptide; about 120 μg/ml of the second polypeptide; about 2.8 molar ratio of polysorbate-80; about 0.5 mg/ml aluminum; about 10 mM histidine; and about 150 mM sodium chloride.4. The composition according to claim 2 , wherein the composition comprises about 60 μg of the first polypeptide; about 60 μg of the second polypeptide; about 18 μg polysorbate-80; about 250 μg aluminum; about 780 μg histidine; and about 4380 μg sodium chloride.5. The composition according to claim 1 , wherein the composition induces a bactericidal titer of serum immunoglobulin that is at least greater than 1-fold higher in the human after receiving the first dose than ...

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15-03-2018 дата публикации

METHOD OF DETECTING NEW IMMUNOGENIC T CELL EPITOPES AND ISOLATING NEW ANTIGEN-SPECIFIC T CELL RECEPTORS BY MEANS OF AN MHC CELL LIBRARY

Номер: US20180073013A1
Принадлежит:

The present invention relates to the field of immunotherapy, in particular, to adoptive T cell therapy, T cell receptor (TCR) gene therapy and vaccination. The invention provides a method for preparing a nucleic acid encoding the TCR alpha chain construct (TRA) and TCR beta chain construct (TRB) of a TCR construct specific for an epitope from an antigen presented on major histocompatibility complex (MHC), comprising contacting T cells isolated from a donor with a library of artificial antigen presenting cells (APC) comprising cells expressing all MHC I or MHC II alleles present in the donor, preferably, in K562 cells. The TCR construct can be expressed in a T cell, which is useful for adoptive T cell therapy, e.g., of cancer, viral infections or autoimmune diseases. The invention further provides a method for identifying the epitope recognized by said TCR. Immunogenic epitopes recognized by said TCRs can be used to develop vaccine formulations to induce antigen-specific T cell immunity in patients. The invention further provides pairs of two TCR constructs and respective immunogenic epitopes obtained by the method of the invention, wherein the epitopes are from human papillomavirus (HPV) 16 (also designated alphapapillomavirus 9) oncoprotein E5 and human cytomegalovirus (CMV) protein pp65. 1. A nucleic acid encoding a T cell receptor (TCR) alpha chain construct (TRA) and/or TCR beta chain construct (TRB) of a TCR construct specific for an epitope in complex with a human MHC I , wherein the epitope is an epitope of human papillomavirus 16 oncoprotein E5 ,wherein the nucleic acid is preferably obtainable from a method comprising(a) stimulating T cells isolated from a donor with professional antigen presenting cells presenting epitopes of said defined antigen and sharing at least one MHC allele with the donor, to enrich antigen-specific T cells; and(b) contacting said T cells with a library of cells, wherein each cell expresses a single MHC allele, wherein the library ...

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05-06-2014 дата публикации

Fusion proteins for use as immunogenic enhancers for inducing antigen-specific t cell responses

Номер: US20140154280A1
Принадлежит: TheVax Genetics Vaccine Co Ltd

A vaccine composition comprising a fusion protein for inducing enhanced pathogen antigen-specific T cell responses is disclosed. The fusion protein comprises: (a) an antigen-presenting cell (APC)-binding domain or a CD91 receptor-binding domain, located at the N-terminus of the fusion protein; (b) a translocation peptide of 34-112 amino acid residues in length, comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 4, 2, 3, or 6, located at the C-terminus of the APC-binding domain or the CD91 receptor-binding domain; and (c) an antigen of a pathogen, located at the C-terminus of the translocation peptide; (d) a nuclear export signal, comprising the amino acid sequence of SEQ ID NO: 13; and (e) an endoplasmic reticulum retention sequence, located at the C-terminus of the fusion protein.

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05-06-2014 дата публикации

Fusion proteins for use as immunogenic enhancers for inducing antigen-specific t cell responses

Номер: US20140154285A1
Принадлежит: TheVax Genetics Vaccine Co Ltd

A fusion protein for use as an immunogen enhancer for enhancing antigen-specific T cell responses is disclosed. The fusion protein comprises: (a) an antigen-presenting cell (APC)-binding domain or a CD91 receptor-binding domain; (b) a protein transduction domain; and (c) an antigen of a pathogen, wherein the APC-binding domain or the CD91 receptor-binding domain is located at the N-terminus of the fusion protein, and the antigen of the pathogen is located at the C-terminus of the protein transduction domain. The protein transduction domain is selected from the group consisting of: (i) a fusion polypeptide, comprising a T cell sensitizing signal-transducing peptide, a linker, and a translocation peptide; (ii) a T cell-sensitizing signal-transducing peptide; and (iii) a translocation peptide of 34-112 amino acid residues in length.

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18-03-2021 дата публикации

INHIBITION OF INNATE IMMUNE RESPONSE

Номер: US20210079346A1
Принадлежит:

The present invention provides methods, kits, and compositions for reducing an innate immune system response in a human or animal cell, tissue or organism. One embodiment comprises: introducing an Agent mRNA comprising in vitro-synthesized mRNA encoding one or more proteins that affect the induction, activity or response of an innate immune response pathway; whereby, the innate immune response in the cell, tissue or organism is reduced compared to the innate immune response in the absence of the Agent mRNA. Other embodiments are methods, compositions and kits for using an Agent mRNA for treating a disease or medical condition in a human or animal that exhibits symptoms of an elevated innate immune system, or for reducing an innate immune response that is induced in a human or animal cell, tissue or organism by a Foreign Substance that is administered to the cell, tissue or organism. 1. A method for reducing an innate immune response in a human or animal cell , tissue or organism , comprising:introducing into the cell, tissue or organism an Agent mRNA comprising in vitro-synthesized mRNA encoding one or more proteins that affect the induction, activity and/or response of an innate immune response pathway;whereby the innate immune response in the cell, tissue or organism is reduced compared to the innate immune response that results or would have resulted in the absence of introducing said Agent mRNA.2. The method of claim 1 , wherein said Agent mRNA encodes one or more proteins that inhibits the activity of an innate immune effector protein in a signaling pathway mediated by a TLR 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 and TLR10 claim 1 , or a biologically active fragment claim 1 , analog or variant of any of said effector proteins.3. The method of claim 1 , wherein said Agent mRNA encodes one or more proteins that is a regulator or inhibitor of ...

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22-03-2018 дата публикации

MACROPHAGE ACTIVATING FACTOR FOR TREATING BENIGN OR PRECANCEROUS PAPILLOMAS

Номер: US20180078613A1
Принадлежит: EFRANAT LTD.

Provided are pharmaceutical compositions including macrophage activating factor derived from Gc protein (GcMAF) for use in treating benign or precancerous papillomas. Further provided are pharmaceutical compositions including GcMAF for use in treating recurrent respiratory papillomatosis (RRP). 125.-. (canceled)26. A method of treating benign or precancerous papilloma comprising administering to a subject in need of such treatment a pharmaceutical composition comprising a therapeutically effective amount of a macrophage activating factor derived from Gc protein (GcMAF) , or a biologically active fragment thereof , and a pharmaceutically acceptable carrier.27. The method according to claim 26 , wherein the benign or precancerous papilloma is selected from the group consisting of laryngeal papilloma (recurrent respiratory papillomatosis) claim 26 , oral papilloma claim 26 , conjuctival papilloma claim 26 , verrucae plantares claim 26 , verrucae vulgaris claim 26 , anogenital warts claim 26 , and focal epithelial hyperplasia.28. The method according to claim 27 , wherein the benign or precancerous papilloma is laryngeal papilloma (recurrent respiratory papillomatosis; RRP).29. The method according to claim 28 , wherein the RRP is juvenile RRP (JRRP).30. The method according to claim 29 , wherein the JRRP is selected from the group consisting of moderate JRRP and aggressive JRRP.31. The method according to claim 30 , wherein the JRRP is aggressive JRRP.32. The method according to claim 28 , wherein the RRP is adult-onset RRP.33. The method according to claim 32 , wherein the adult-onset RRP is aggressive adult-onset RRP.34. The method according to claim 26 , wherein GcMAF comprises the amino acid sequence as set forth in any one of SEQ ID NOs:1-3 or a biologically active fragment thereof.35. The method according to claim 34 , wherein GcMAF consists of the amino acid sequence as set forth in any one of SEQ ID NOs:1-3.36. The method according to claim 26 , wherein the ...

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22-03-2018 дата публикации

ISG15 AND ITS USE AS AN ADJUVANT

Номер: US20180078638A1
Принадлежит:

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 ...

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23-03-2017 дата публикации

METHODS AND COMPOSITIONS FOR INCREASING A T-EFFECTOR CELL TO REGULATORY T CELL RATIO

Номер: US20170080064A1
Принадлежит:

The present invention is directed to methods for increasing T-cell effector cell to regulatory T cell ratio. The invention is further directed to methods of treating, protecting against, and inducing an immune response against a tumor, comprising the step of administering to a subject a recombinant strain, comprising a fusion peptide that comprises an LLO fragment and tumor-associated antigen. 1ListeriaListeria. A method of eliciting an anti-tumor T cell response in a subject having a tumor or cancer , comprising the step of administering to said subject a recombinant strain comprising a recombinant nucleic acid , said nucleic acid molecule comprising a first open reading frame encoding a recombinant polypeptide and a second open reading frame second open reading frame encoding a metabolic , wherein said recombinant polypeptide comprises a truncated LLO protein fused to a heterologous antigen or fragment thereof , wherein said comprises a mutation in the endogenous alanine racemase gene (dal) , D-amino acid transferase gene (dat) , and actA genes , and wherein said T-cell response comprises increasing a ratio of T effector cells to regulatory T cells (Tregs) , thereby eliciting an anti-tumor T cell response in said subject.2. The method of claim 1 , wherein said tumor-associated antigen is a human papilloma virus E7 antigen.3. The method of any one of - claim 1 , wherein said truncated LLO protein is an N-terminal LLO.4. The method of claim 2 , wherein said LLO is set forth in SEQ ID NO: 2.5. The method of any one of - claim 2 , wherein said heterologous antigen is a tumor-associated antigen.6. The method of any one of - claim 2 , wherein said tumor-associated antigen is an angiogenic antigen.7Listeria. The method of any one of - claim 2 , wherein said lacks antibiotic resistance genes.8Listeria.. The method of any one of - claim 2 , wherein said recombinant nucleic acid is in a plasmid in said9. The method of claim 8 , wherein said plasmid is an episomal plasmid.10 ...

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25-03-2021 дата публикации

PD1 AND PDL1 ANTIBODIES AND VACCINE COMBINATIONS AND USE OF SAME FOR IMMUNOTHERAPY

Номер: US20210085779A1
Принадлежит:

Disclosed herein is a vaccine comprising an antigen and PD1 antibody and/or PDL1 antibody. Also disclosed herein is a method for enhancing an immune response in a subject. The method may comprise administering the vaccine to the subject in need thereof. 1. A composition for enhancing an immune response against an antigen in a subject in need thereof , comprising:a) PD1 antibody or PDL1 antibody, or combination thereof, andb) a synthetic antigen capable of generating an immune response in the subject, or an immunogenic fragment or variant thereof.2. The composition of wherein the synthetic antigen is an isolated DNA that encodes for the antigen.3Plasmodium falciparumC. difficle.. The composition of wherein the synthetic antigen is selected from the group consisting of: hTERT claim 2 , prostate claim 2 , WT1 claim 2 , tyrosinase claim 2 , NYES01 claim 2 , PRAME claim 2 , MAGE claim 2 , CMV claim 2 , herpes claim 2 , HIV claim 2 , HPV claim 2 , HCV claim 2 , HBV claim 2 , influenza claim 2 , RSV claim 2 , claim 2 , and4. The composition of claim 3 , wherein the HPV antigen is E6 and E7 domains of subtypes selected from the group consisting of: HPV6 claim 3 , HPV11 claim 3 , HPV18 claim 3 , HPV31 claim 3 , HPV33 claim 3 , HPV52 claim 3 , and HPV58 claim 3 , and a combination thereof.5. The composition of claim 3 , wherein the HIV antigen is selected from the group consisting of: Env A claim 3 , Env B claim 3 , Env C claim 3 , Env D claim 3 , B Nef-Rev claim 3 , and Gag claim 3 , and a combination thereof.6. The composition of claim 3 , wherein the influenza antigen is selected from the group consisting of: H1 HA claim 3 , H2 HA claim 3 , H3 HA claim 3 , H5 HA claim 3 , BHA antigen claim 3 , and any combination thereof.7Plasmodium falciparum. The composition of claim 3 , wherein the antigen includes a circumsporozoite (CS) antigen.8C. difficle. The composition of claim 3 , wherein the antigen is selected from the group consisting of: Toxin A claim 3 , and Toxin B claim 3 ...

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21-03-2019 дата публикации

VIRUS-LIKE PARTICLE CONJUGATES FOR DIAGNOSIS AND TREATMENT OF TUMORS

Номер: US20190083647A1
Принадлежит:

The present disclosure is directed to methods and compositions for the diagnosis and/or treatment of tumors, such as ocular tumors, using virus-like particles conjugated to photosensitive molecules. 184.-. (canceled)84. A method of producing tumor-targeting papilloma virus-like particles bioconjugates , the method comprising:(a) transfecting mammalian cells in vitro with deoxyribonucleic acid encoding papilloma virus capsid proteins;(b) purifying the capsid proteins through chromatographic steps;(c) conjugating about 50 to about 1000 near infrared phthalocyanine dye molecules to papilloma virus capsid proteins, wherein the near infrared phthalocyanine dye molecules become toxic or produce a toxic molecule upon light activation.85. The method of further comprising treating the viral capsids of step (a) with benzonase or other agents to eliminate host cell DNA claim 84 ,86. The method of claim 84 , wherein the papilloma virus capsid proteins are human papilloma virus (HPV) capsid proteins.87. The method of claim 86 , wherein the HPV capsid proteins comprise HPV L1 capsid proteins claim 86 , HPV L2 capsid proteins claim 86 , or a combination of HPV L1 capsid proteins and HPV L2 capsid proteins.88. The method of claim 87 , wherein the HPV L1 capsid proteins comprise an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 1.89. The method of claim 84 , wherein the papilloma virus capsid proteins are non-human papilloma virus capsid proteins.90. The method of claim 89 , wherein the non-human papilloma virus capsid proteins are bovine papilloma virus (BPV) capsid proteins.91. The method of claim 90 , wherein the BPV capsid proteins comprise BPV L1 capsid proteins claim 90 , BPV L2 capsid proteins claim 90 , or a combination of BPV L1 capsid proteins and BPV L2 capsid proteins.92. The method of claim 91 , wherein the BPV L1 capsid proteins comprise an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 2.93. The method of claim 84 , wherein ...

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31-03-2016 дата публикации

ORAL VACCINE HAVING IMPROVED CELLULAR IMMUNITY INDUCTION POTENCY

Номер: US20160089429A1
Принадлежит:

An oral preparation for the prophylaxis or treatment of a disease with infection by a pathogen, containing a killed lactic acid bacterium expressing, on the surface, an antigen of the pathogen, or a microparticulated form thereof, which has an average particle size of 2.68-30 μm. An oral preparation for inducing cellular immunity to a target antigen, containing a killed lactic acid bacterium expressing the target antigen on the surface or a microparticulated form thereof, which has a particle size of 2.68-30 μm. 1. An oral preparation for the prophylaxis or treatment of a disease with infection by a pathogen , comprising a killed lactic acid bacterium expressing , on the surface , an antigen of the pathogen , or a microparticulated form thereof , which has an average particle size of 2.68-30 μm.2. The oral preparation according to claim 1 , wherein the pathogen is an intracellular infectious pathogen.3. The oral preparation according to claim 2 , wherein the intracellular infectious pathogen is a virus.4. The oral preparation according to claim 3 , wherein the virus is human papilloma virus.5. The oral preparation according to claim 1 , wherein the antigen of the pathogen is an internal antigen of the pathogen.6. The oral preparation according to claim 5 , wherein the antigen of the pathogen is E7.7. The oral preparation according to for the prophylaxis or treatment of the disease with infection by the pathogen by inducing cellular immunity to the antigen of the pathogen.8. An oral preparation for inducing cellular immunity to a target antigen claim 1 , comprising a killed lactic acid bacterium expressing the target antigen on the surface or a microparticulated form thereof claim 1 , which has an average particle size of 2.68-30 μm.9. The oral preparation according to claim 8 , wherein the target antigen is an antigen of a pathogen.10. The oral preparation according to claim 9 , wherein the pathogen is an intracellular infectious pathogen.11. The oral preparation ...

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19-03-2020 дата публикации

PHARMACEUTICAL COMPOSITION COMPRISING A POLYMERIC CARRIER CARGO COMPLEX AND AT LEAST ONE PROTEIN OR PEPTIDE ANTIGEN

Номер: US20200085943A1
Принадлежит: CureVac AG

The present invention is directed to a pharmaceutical composition including (e.g. for use as an adjuvant) a polymeric carrier cargo complex, comprising as a carrier a polymeric carrier formed by disulfide-crosslinked cationic components; and as a cargo at least one nucleic acid molecule, and at least one antigen that is selected from an antigen from a pathogen associated with infectious disease; an antigen associated with allergy or allergic disease; an antigen associated with autoimmune disease; or an antigen associated with a cancer or tumour disease, or in each case a fragment, variant and/or derivative of said antigen. The pharmaceutical composition allows for efficient induction of an adaptive immune response directed against said antigen. The present invention furthermore provides kits, as well as the use of the pharmaceutical composition or the kit as a vaccine, particularly in the treatment of infectious diseases, allergies, autoimmune diseases and tumour or cancer diseases. 1. A method of inducing an immune response to an antigen , the method comprising administering to a subject in need thereof a pharmaceutical composition comprising: a) a polymeric carrier comprising disulfide-crosslinked cationic peptides, as a carrier; and', 'b) at least one immunostimulatory RNA (isRNA) molecule as a cargo,, '(A) a polymeric carrier cargo complex, comprisingand a) an antigen from a pathogen associated with infectious disease;', 'b) an antigen associated with allergy or allergic disease;', 'c) an antigen associated with autoimmune disease; and', 'd) an antigen associated with a cancer or tumour disease., '(B) at least one protein or peptide antigen that is selected from the group consisting of2. The method of claim 1 , wherein component (B) is not covalently linked to component (A).3Bacillus anthracisMycobacterium tuberculosis.. The method of claim 1 , wherein said protein or peptide antigen is from a pathogen selected from the list consisting of: Rabies virus claim 1 , ...

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05-05-2022 дата публикации

VIRUS-INSPIRED COMPOSITIONS AND METHODS OF REDIRECTING PREEXISTING IMMUNE RESPONSES USING THE SAME FOR TREATMENT OF CANCER

Номер: US20220135624A1
Принадлежит:

Disclosed are virus-inspired compositions and preparation methods thereof, where the compositions comprise mutant papillomavirus L1 proteins that spontaneously form capsid backbones and that are conjugated to a peptide comprising an epitope to form immune redirector capsids (IRCs). The epitopes on the peptides are designed to be recognized by a subject's immune system based on the subject's preexisting immune memory developed from the subject's past exposure to the epitope through infection or vaccination. The mutant papillomavirus L1 proteins possess three mutations including an amino-terminal truncation, a carboxy-terminal truncation, and a truncation at helix four. These mutations in the L1 protein yield capsomeres that are form non-canonical T=1 geometry capsid backbones. Disclosed are uses and methods of using the compositions in treating and/or preventing cancers in subjects in need thereof.

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07-04-2016 дата публикации

DPS FUSION PROTEINS FOR USE IN VACCINES AND DIAGNOSTICS

Номер: US20160095917A1
Автор: Ni Yawei
Принадлежит:

Novel nanoparticle fusion proteins comprising proteins or peptides fused to Dps (DNA binding protein from starved cells) proteins are provided which bring forth distinct advantages for development of new and improved vaccines, diagnostic tests, and other biomedical products. 1. A Dps fusion protein comprising two proteins or peptides fused separately and simultaneously to the N-terminus and C-terminus of Dps , wherein said Dps fusion protein is capable of self-assembly into nanoparticles and said proteins or peptides are presented on the outer surface of said Dps fusion protein.2. The Dps fusion protein of claim 1 , wherein said Dps fusion protein further comprises one protein or peptide fused to an internal site of Dps.3. The Dps fusion protein of claim 1 , wherein said proteins or peptides are derived from a group of proteins or peptides comprising M2e and HA2 of influenza virus claim 1 , L2 of papillomavirus claim 1 , gp41 of human immunodeficiency virus claim 1 , and WT1 protein of cancers.4. The Dps fusion protein of claim 1 , wherein said proteins or peptides comprise a viral fusion peptide.5. The Dps fusion protein of claim 3 , wherein said Dps fusion protein is soluble.6. The Dps fusion protein of claim 1 , wherein said proteins or peptides comprise a trimer-forming protein or peptide.7. The Dps fusion protein of claim 1 , wherein said proteins or peptides are M2e and fusion peptide of influenza virus.8. The Dps fusion protein of claim 1 , wherein said Dps fusion protein comprises the amino acid sequence of SEQ ID No: 3 claim 1 , 6 claim 1 , or 7 claim 1 , wherein said Dps is optionally substituted with Dps from a different bacterium or archaeon.9. The Dps fusion protein of claim 1 , wherein said Dps fusion protein is thermostable.10. The Dps fusion protein of claim 9 , wherein said Dps is derived from a mesophile.11. The Dps fusion protein of claim 1 , wherein said Dps fusion protein is covalently conjugated with the alpha Gal epitope or its analog.12. The ...

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09-04-2015 дата публикации

Mucosal Immunity-Stimulating Agent, and Oral Pharmaceutical Composition for Treating HPV Infection

Номер: US20150098959A1
Автор: Ayumi TAGUCHI, Kei KAWANA
Принадлежит:

A mucosal immunity-stimulating agent contains a Kampo preparation having a revitalizing activity and a mucosal adjuvant. An oral pharmaceutical composition for treating HPV infection contains at least HPV E7 polypeptide and a Kampo preparation having a revitalizing activity. 1. A mucosal immunity-stimulating agent , comprising:a Kampo preparation having a revitalizing activity; anda mucosal adjuvant.2. The mucosal immunity-stimulating agent according to claim 1 , wherein the Kampo preparation having a revitalizing activity is Juzentaihoto claim 1 , Hochuekkito claim 1 , or both thereof.3E. coli. The mucosal immunity-stimulating agent according to claim 1 , wherein the mucosal adjuvant is a polypeptide claim 1 , a synthetic ceramide (αGalCer) claim 1 , or both thereof claim 1 , and wherein the polypeptide is selected from the group consisting of a wild-type polypeptide derived from a cholera toxin (CT) claim 1 , a heat-labile enterotoxin from (LT) claim 1 , a verotoxin (VT) claim 1 , a diphteria toxin (DT) claim 1 , or a pertussis toxin (PT) claim 1 , and mutant polypeptides thereof.4. The mucosal immunity-stimulating agent according to claim 3 , wherein the mucosal adjuvant is a polypeptide derived from a B subunit of the LT (LTB) or the synthetic ceramide (αGalCer).5. The mucosal immunity-stimulating agent according to claim 1 , wherein claim 1 , in the case of oral administration claim 1 , the mucosal immunity-stimulating agent stimulates cellular immunity specific for an antigen orally administered before claim 1 , after claim 1 , or concurrently with it claim 1 , in a mucosa of a patient.6. The mucosal immunity-stimulating agent according to claim 5 , wherein the antigen is a polypeptide derived from a human papillomavirus (HPV).7. The mucosal immunity-stimulating agent according to claim 6 , wherein the polypeptide derived from HPV has a mutation in which one to several amino acids are deleted claim 6 , substituted claim 6 , or added.8Lactobacillus ...

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12-05-2022 дата публикации

Cd40 ligand fusion protein vaccine

Номер: US20220143171A1
Принадлежит: Microvax LLC

Provided are methods of generating an immune response to any of various antigens including foreign antigens such as infectious agent antigens. In general, the method comprises administering an expression vector encoding a transcription unit encoding a secretable fusion protein, the fusion protein containing the foreign antigen and CD40 ligand and also administering the encoded fusion protein. In another approach, an immune response to the foreign antigen is elicited using the encoded fusion protein without administering the vector. The invention methods may be used to immunize an individual against an infectious agent such as influenza virus. Methods of obtaining an immune response in older individuals also is described.

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01-04-2021 дата публикации

Bispecific Molecules That Are Immunoreactive With Immune Effector Cells That Express An Activating Receptor And An Antigen Expressed By A Cell Infected By A Virus And Uses Thereof

Номер: US20210095021A1
Принадлежит:

The present invention relates to bispecific molecules that are capable of localizing an immune effector cell that expresses an activating receptor to a virally infected cell, so as to thereby facilitate the killing of the virally infected cell. In a preferred embodiment, such localization is accomplished using bispecific molecules that are immunoreactive with an activating receptor of an immune effector cell and to an antigen expressed by a cell infected with a virus wherein the antigen is detectably present on the cell infected with the virus at a level that is greater than the level at which the antigen is detected on the virus by the bispecific molecules, and to the use of such bispecific molecules in the treatment of latent viral infections. 130-. (canceled)31. A bispecific diabody comprising first and second polypeptide chains , wherein: (i) a domain (A) comprising a binding region of a light chain variable domain of a first immunoglobulin (VL1) specific for an HIV epitope;', '(ii) a domain (B) comprising a binding region of a heavy chain variable domain of a second immunoglobulin (VH2) specific for a CD3 epitope; and', '(iii) a domain (C);, '(A) the first polypeptide chain comprises, in the N-terminal to C-terminal direction (i) a domain (D) comprising a binding region of a light chain variable domain of the second immunoglobulin (VL2) specific for the CD3 epitope;', '(ii) a domain (E) comprising a binding region of a heavy chain variable domain of the first immunoglobulin (VH1) specific for the HIV epitope;', '(iii) a domain (F);, '(B) the second polypeptide chain comprises, in the N-terminal to C-terminal direction (ii) domains (D) and (E) do not associate with one another to form an epitope-binding domain;', '(iii) domains (A) and (E) associate to form an epitope-binding domain that binds the HIV epitope, and domains (B) and (D) associate to form an epitope-binding domain that binds the CD3 epitope,', '(iv) domains (C) and (F) are covalently associated ...

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06-04-2017 дата публикации

IMMUNOGENIC HPV L2-CONTAINING VLPS AND RELATED COMPOSITIONS, CONSTRUCTS, AND THERAPEUTIC METHODS

Номер: US20170096456A1
Принадлежит:

The invention provides immunotherapeutic and prophylactic bacteriophage viral-like particle (VLPs) which are useful in the treatment and prevention of human papillomavirus (HPV) infections and related disorders, including cervical cancer and persistent infections associated with HPV. Related compositions (e.g. vaccines), nucleic acid constructs, and therapeutic methods are also provided. VLPs and related compositions of the invention induce high titer antibody responses against HPV L2 and protect against HPV challenge in vivo. VLPs, VLP-containing compositions, and therapeutic methods of the invention induce an immunogenic response against HPV infection, confer immunity against HPV infection, protect against HPV infection, and reduce the likelihood of infection by HPV infection. 1107-. (canceled)108. A RNA bacteriophage particle comprising a RNA bacteriophage single chain coat polypeptide dimer having a heterologous peptide displayed on the surface of the particle , the heterologous peptide comprising an immunogenic peptide consisting of an amino acid sequence corresponding to amino acids 17-31 of the Human Papillomavirus (HPV) 16 L2 protein.109. The RNA bacteriophage particle of claim 108 , wherein heterologous peptide comprises two immunogenic HPV peptides.110. The RNA bacteriophage particle of claim 109 , wherein the two immunogenic HPV peptides are from different HPV strains.111. The RNA bacteriophage particle of claim 108 , wherein the immunogenic peptide is from HPV1 claim 108 , HPV5 claim 108 , HPV8 claim 108 , HPV31 claim 108 , HPV35 claim 108 , HPV33 claim 108 , HPV58 claim 108 , HPV52 claim 108 , HPV73 claim 108 , HPV6 claim 108 , HPV11 claim 108 , HPV18 claim 108 , HPV45 claim 108 , HPV39 claim 108 , HPV68 claim 108 , HPV59 claim 108 , HPV51 claim 108 , HPV56 claim 108 , HPV66 claim 108 , or HPV2.112. An immunogenic composition comprising an RNA bacteriophage particle of .113. A method for inducing an immune response to HPV in a subject comprising ...

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06-04-2017 дата публикации

CYAA-BASED CHIMERIC PROTEINS COMPRISING A HETEROLOGOUS POLYPEPTIDE AND THEIR USES IN THE INDUCTION OF IMMUNE RESPONSES

Номер: US20170096458A1
Принадлежит: GENTICEL

The invention relates to a chimeric protein comprising or consisting of, from N-terminal to C-terminal, (a) a N-terminal part of a CyaA protein (b) a heterologous polypeptide, and (c) a C-terminal part of a CyaA protein. The invention also relates to a polynucleotide encoding a deleted version of a CyaA, as well as a polynucleotide encoding this chimeric protein. A composition comprising at least one chimeric protein(s) of the invention and the prophylactic and/or therapeutic uses of said composition are also part of the invention. 1. A CyaA-derived protein encoded by a polynucleotide comprising or consisting of:{'i': 'Bordetella pertussis', '1) a fragment of the CyaA protein as set forth in SEQ ID NO: 2, wherein said fragment consists of the sequence beginning with the first residue of SEQ ID NO:2 and ending with a residue located from position 183 to position 227 of SEQ ID NO:2 or a variant thereof, wherein said variant has at least 95% similarity with said fragment, fused to'}{'i': 'Bordetella pertussis', '2) a fragment of the CyaA protein as set forth in SEQ ID NO: 2, wherein said fragment consists of the sequence beginning with a residue located from position 321 to position 387 of SEQ ID NO:2 and ending with the last residue of SEQ ID NO:2, or a variant wherein said variant has at least 95% similarity with said fragment, wherein said CyaA-derived protein keeps the capacity of CyaA to bind to CD11b-expressing cells as target cells and/or to translocate its adenylate cyclase domain into the cytosol of said target cells and wherein the CyaA-derived protein is devoid of enzymatic activity of CyaA.'}2. The CyaA-derived protein according to claim 1 , which is selected from the group consisting of:1) a polypeptide comprising or consisting of the sequence as set forth in SEQ ID NO:10 or a variant thereof, wherein said variant has at least 95% similarity with this polypeptide;2) a polypeptide comprising or consisting of the sequence as set forth in SEQ ID NO:12 or a ...

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08-04-2021 дата публикации

CATIONIC LIPID VACCINE COMPOSITIONS AND METHODS OF USE

Номер: US20210100898A1
Принадлежит:

The present disclosure provides vaccine compositions comprising at least one adjuvant and at least one therapeutic factor. The disclosure also provides methods of reducing an immune suppressor cell population in a mammal, methods of argumenting an immune response in a mammal, and methods of treating a diseases in a mammal utilizing the vaccine compositions. 1. A method of reducing an immune suppressor cell population in a mammal , said method comprising the step of administering an effective amount of a composition to the mammal , wherein the composition comprises an adjuvant and a therapeutic factor , and wherein the adjuvant is a cationic lipid.2. The method of claim 1 , wherein the immune suppressor cell is MDSC.3. The method of claim 1 , wherein the cationic lipid is selected from the group consisting of DOTAP claim 1 , DOTMA claim 1 , DOEPC claim 1 , and combinations thereof.4. The method of claim 1 , wherein the cationic lipid is DOTAP.5. The method of claim 1 , wherein the adjuvant is an enantiomer of the cationic lipid.6. The method of claim 5 , wherein the enantiomer is R-DOTAP.7. The method of claim 1 , wherein the therapeutic factor is a cytokine claim 1 , and wherein the cytokine is GM-CSF.8. The method of claim 1 , wherein the composition further comprises one or more antigens.9. The method of claim 8 , wherein at least one antigen is an HPV protein or peptide.10. The method of claim 9 , wherein the antigens comprise one or more of the gp100 sequence (KVPRNQDWL [SEQ. ID. No. 8]) and the TRP2 sequence (SYVDFFVWL [SEQ. ID. No. 9]).11. A method of augmenting an immune response in a mammal claim 9 , said method comprising the step of administering an effective amount of a vaccine composition to the mammal claim 9 , wherein the vaccine composition comprises an adjuvant and a therapeutic factor claim 9 , and wherein the adjuvant is a cationic lipid.12. The method of claim 11 , wherein the reduction results in an increase in T-cell response in the mammal.13. ...

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08-04-2021 дата публикации

NEISSERIA MENINGITIDIS COMPOSITIONS AND METHODS THEREOF

Номер: US20210101943A1
Принадлежит:

In one aspect, the invention relates to a composition including a first polypeptide having the sequence set forth in SEQ ID NO: 1 and a second polypeptide having the sequence set forth in SEQ ID NO: 2. In one embodiment, the composition includes about 120 μg/ml of a first polypeptide including the amino acid sequence set forth in SEQ ID NO: 1, 120 μg/ml of a second polypeptide including the amino acid sequence set forth in SEQ ID NO: 2, about 2.8 molar ratio polysorbate-80 to the first polypeptide, about 2.8 molar ratio polysorbate-80 to the second polypeptide, about 0.5 mg/ml aluminum, about 10 mM histidine, and about 150 mM sodium chloride. In one embodiment, a dose of the composition is about 0.5 ml in total volume. In one embodiment, two-doses of the composition induce a bactericidal titer against diverse heterologous subfamily A and subfamily B strains in a human. 1Neisseria meningitidisNeisseria meningitidis. A method of inducing a bactericidal immune response in a human against a serogroup B subfamily A strain and against a serogroup B subfamily B strain , comprising administering to the human an effective amount of a composition comprising a) a first lipidated polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 1 , and b) a second lipidated polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 2; wherein the method further comprises administering to the human an immunogenic composition against human papillomavirus.2Neisseria meningitidis.. The method according to claim 1 , wherein the immunogenic composition against human papillomavirus is administered to the human within 24 hours of administering said composition against3. The method according to claim 1 , further comprising inducing an immune response against any one of human papillomavirus types 6 claim 1 , 11 16 claim 1 , 18 claim 1 , or any combination thereof. The present application is a continuation application of U.S. patent application Ser. No. 15/728,610, filed ...

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21-04-2016 дата публикации

VACCINE COMPOSITION

Номер: US20160106820A1
Принадлежит:

There is described a kit for use in inducing an immune response in a mammal, the kit includes: a first virus that expresses MAGEA3, Human Papilloma Virus E6/E7 fusion protein, human Six-Transmembrane Epithelial Antigen of the Prostate protein, or Cancer Testis Antigen 1, or a variant thereof as an antigenic protein and that is formulated to generate an immunity to the protein or variant thereof in the mammal. The kit also includes a Maraba MG1 virus encoding the same antigen, or a variant of the same antigen. The Maraba MG1 virus is formulated to induce the immune response in the mammal. The first virus is immunologically distinct from the Maraba MG1 virus. 1. A kit for use in inducing an immune response in a mammal , the kit comprising:a first virus that expresses a protein comprising an amino acid sequence of SEQ ID NO: 1, or a variant thereof, as an antigenic protein and that is formulated to generate an immunity to the protein or variant thereof in the mammal; anda Maraba MG1 virus encoding a protein comprising an amino acid sequence SEQ ID NO: 1, or a variant thereof, as an antigenic protein, the Maraba MG1 virus formulated to induce the immune response in the mammal;the first virus being immunologically distinct from the Maraba MG1 virus.2. The kit according to claim 1 , wherein the antigenic protein expressed by the first virus and the antigenic protein expressed by the Maraba MG1 virus are identical.3. The kit according to claim 1 , wherein the first virus claim 1 , the Maraba MG1 virus claim 1 , or both claim 1 , are formulated for administration as isolated viruses.4. The kit according to claim 1 , whereinthe Maraba MG1 virus includes a reverse complement and RNA version of a transgene comprising a nucleotide sequence of SEQ ID NO: 2;the first virus is a negative strand RNA virus and includes a reverse complement and RNA version of a transgene comprising a nucleotide sequence of SEQ ID NO: 2;the first virus is a DNA virus or a positive sense RNA virus and ...

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23-04-2015 дата публикации

METHOD OF VACCINATION AGAINST HUMAN PAPILLOMAVIRUS

Номер: US20150110824A1
Принадлежит:

The disclosure provides immunogenic compositions comprising HPV VLPs from one or more HPV types in combination with an adjuvant comprising a TLR agonist for use in a method for the prevention of HPV infection or disease in an individual, wherein a first dose of the immunogenic composition comprising HPV VLPs and a TLR agonist, is administered followed by a second dose of an immunogenic composition comprising HPV VLPs from one or more HPV types but which does not comprise a TLR agonist. 12-. (canceled)3. A method for the prevention of HPV infection or disease in an individual , which method comprises:(i) administering to the individual at least one dose of a first immunogenic composition comprising HPV VLPs from one or more HPV types in combination with an adjuvant comprising a TLR agonist; and(ii) administering to the individual at least one dose of a second immunogenic composition comprising HPV VLPs from one or more HPV types which second immunogenic composition does not comprise a TLR agonist;wherein the first immunogenic composition increases at least one of a type specific immune response or cross-reactive immune response to a type present in the second immunogenic composition, which is not present in the first immunogenic composition.4. The method of wherein the first immunogenic composition comprises HPV 16 or HPV 18 VLPs claim 3 , or HPV 16 and HPV 18 VLPs.5. The method according to wherein the first immunogenic composition increases the type specific immune response to HPV 16 or HPV 18 or both HPV 16 and HPV 18.6. The method of wherein the first immunogenic composition increases the type specific immune response compared to the immune response to that HPV type when an equivalent number of doses of only the second immunogenic composition are administered.7. The method of wherein the first immunogenic composition generates a cross reactive immune response against one or more high risk or low risk HPV types present in the second immunogenic composition.8. ( ...

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30-04-2015 дата публикации

PHARMACEUTICAL COMPOSITION COMPRISING A POLYMERIC CARRIER CARGO COMPLEX AND AT LEAST ONE PROTEIN OR PEPTIDE ANTIGEN

Номер: US20150118264A1
Принадлежит: CUREVAC GMBH

The present invention is directed to a pharmaceutical composition including (e.g. for use as an adjuvant) a polymeric carrier cargo complex, comprising as a carrier a polymeric carrier formed by disulfide-crosslinked cationic components; and as a cargo at least one nucleic acid molecule, and at least one antigen that is selected from an antigen from a pathogen associated with infectious disease; an antigen associated with allergy or allergic disease; an antigen associated with autoimmune disease; or an antigen associated with a cancer or tumour disease, or in each case a fragment, variant and/or derivative of said antigen. The pharmaceutical composition allows for efficient induction of an adaptive immune response directed against said antigen. The present invention furthermore provides kits, as well as the use of the pharmaceutical composition or the kit as a vaccine, particularly in the treatment of infectious diseases, allergies, autoimmune diseases and tumour or cancer diseases. 1. A pharmaceutical composition comprising: a) a polymeric carrier comprising disulfide-crosslinked cationic components, preferably formed by disulfide-crosslinked cationic components, as a carrier; and', 'b) at least one nucleic acid molecule as a cargo, and, '(A) a polymeric carrier cargo complex, comprising (i) an antigen from a pathogen associated with infectious disease;', '(ii) an antigen associated with allergy or allergic disease;', '(iii) an antigen associated with autoimmune disease; and', '(iv) an antigen associated with a cancer or tumour disease', 'or a fragment, variant and/or derivative of said protein or peptide antigen., '(B) at least one protein or peptide antigen that is selected from the group consisting of2. The pharmaceutical composition of claim 1 , wherein component (B) is not covalently linked to component (A).3Bacillus anthracisMycobacterium tuberculosis.. The pharmaceutical composition of claim 1 , wherein said protein or peptide antigen is from a pathogen ...

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26-04-2018 дата публикации

Fusion polypeptide for immuno-enhancement and method for enhancing stimulation of immune response using the same

Номер: US20180111964A1
Принадлежит:

A fusion polypeptide is disclosed, which includes: (a) a mucosa targeting polypeptide; (b) a translocating peptide for translocation; and (c) a antigenic epitope. In addition, a method for enhancing a stimulation of an immune response using the aforementioned fusion polypeptide is also disclosed. 1. A fusion polypeptide , comprising:(a) a mucosa targeting polypeptide;(b) a first translocating peptide for translocation; and(c) a first antigenic epitope.2. The fusion polypeptide of claim 1 , wherein the mucosa targeting polypeptide is located at an N-terminal of the fusion polypeptide claim 1 , the first antigenic epitope is located at a C-terminal of the fusion polypeptide claim 1 , and the first translocation peptide is located between the mucosa targeting polypeptide and the first antigenic epitope.3. The fusion polypeptide of claim 1 , wherein the mucosa targeting polypeptide is an M-cell targeting polypeptide or an intestine epithelial targeting polypeptide.4. The fusion polypeptide of claim 1 , wherein the mucosa targeting polypeptide comprises an amino acid sequence selected from SEQ ID NOs: 1 to 4.5pseudomonas. The fusion polypeptide of claim 1 , wherein the first translocating peptide is from exotoxin.6pseudomonas. The fusion polypeptide of claim 1 , wherein the first translocating peptide comprises a exotoxin A fragment deleted of only domain III.7. The fusion polypeptide of claim 1 , wherein the first antigenic epitope is a Th1 antigenic epitope.8. The fusion polypeptide of claim 1 , wherein the first antigenic epitope is an HPV antigenic epitope claim 1 , a Myostatin epitope claim 1 , or a PRRSV antigenic epitope.9. The fusion polypeptide of claim 8 , wherein the HPV antigenic epitope is an E7 peptide sequence or an E6 peptide sequence of human papillomavirus type 16.10. The fusion polypeptide of claim 1 , wherein the first antigenic epitope is selected from SEQ ID NOs: 10 claim 1 , 12 claim 1 , 17 claim 1 , 18 claim 1 , 21 claim 1 , 22 and 23.11. A method ...

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27-04-2017 дата публикации

CELL DELIVERY SYSTEM AND METHOD

Номер: US20170112760A1
Принадлежит:

The present invention is directed to a cell delivery system for the delivery of materials including nucleic acids across a biological barrier and methods of use thereof. The cell delivery system of the invention comprises a microprotrusion array composed of a swellable and/or dissolvable polymer composition for use in the transport of a material across a biological barrier, wherein the material comprises nanoparticles formed from a nucleic acid complexed with an amphipathic cell penetrating peptide and wherein the microprotrusion array is loaded with the nanoparticles. 1. A cell delivery system comprisinga microprotrusion array for use in the transport of a material across a biological barrier in which the array comprises a plurality of microprotrusions composed of a swellable and/or dissolvable polymer composition;the material comprises nanoparticles formed from a nucleic acid or a negatively charged or hydrophilic compound complexed with an amphipathic cell penetrating peptide;wherein the microprotrusion array is loaded with the nanoparticles.2. The cell delivery system according to wherein the nucleic acid comprises a DNA vaccine.3. The cell delivery system according to wherein the nucleic acid is adapted for gene therapy claim 1 , and is optionally a DNA claim 1 , mRNA claim 1 , miRNA or siRNA molecule.4. The cell delivery system according to claim 1 , wherein the amphipathic cell penetrating peptide comprises less than approximately 50 amino acid residues with at least 6 arginine residues (R) claim 1 , at least 12 Alanine Residues (A) claim 1 , at least 6 leucine residues (L) claim 1 , optionally at least one cysteine residue (C) claim 1 , and at least two but no greater than three glutamic acids (E).5. The cell delivery system according to comprising an amphipathic cell penetrating peptide whereinthe arginine (R) residues are evenly distributed along the length of the peptide;the ratio of arginine (R) to negatively charged glutamic acid (E) residues is from at ...

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09-04-2020 дата публикации

LIPID A MIMICS, METHODS OF PREPARATION, AND USES THEREOF

Номер: US20200109160A1
Принадлежит: Immunovaccine Technologies Inc.

The invention provides lipid A mimics in which one or both of the sugar residues of a natural lipid A disaccharide backbone has been replaced with an aromatic group. These lipid A mimics may further differ from a natural lipid A molecule with respect to other structural characteristics, such as, a different number of phosphate groups present, changes in the number, structure and location of lipid chains and/or changes in the spacing and linkage of the sugar residues (or their aromatic replacements). The lipid A mimics may be lipid A agonists and as such may be useful as immunostimulatory agents in inducing or patenting an antibody and/or cell-mediated immune response, or may be lipid A antagonists and as such may be useful in treating or preventing a lipopolysaccharide (LPS)/lipid A-mediated disease or disorder. Also provided are methods for preparing the lipid A mimics. 1. A compound of formula:{'br': None, 'sub': 1', '2, 'A-L-D-L-E'}wherein:A is a cyclic monosaccharide residue with one or more of the hydroxyl groups optionally substituted or absent, or A is a substituted or unsubstituted aromatic group;{'sub': 1', '2, 'Land Lindependently are present or absent, and if present is independently a substituted or unsubstituted, branched or linear, saturated or unsaturated, carbon chain optionally comprising one or more of O, S or N;'}D is —O—, —S— or —NH—; andE is a cyclic monosaccharide residue with one or more of the hydroxyl groups optionally substituted or absent, or E is a substituted or unsubstituted aromatic group;{'sub': 1', '2, 'wherein at least one of A or E is a substituted or unsubstituted aromatic group and at least one of A, L, Lor E comprises one or more lipid chain substituents;'}or a pharmaceutically acceptable salt thereof.3. The compound of or , or pharmaceutically acceptable salt thereof , wherein at least one of A or E is a substituted or unsubstituted monocyclic carbocyclic aromatic group or a substituted or unsubstituted monocyclic ...

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07-05-2015 дата публикации

METHODS FOR CONSTRUCTING ANTIBIOTIC RESISTANCE FREE VACCINES

Номер: US20150125480A1
Принадлежит:

The present invention provides vaccine strains that express a heterologous antigen and a metabolic enzyme, and methods of generating same. 134-. (canceled)35ListeriaListeriaListeria. A method of inducing an immune response against a tumor or cancer in a subject , said method comprising the step of administering to the subject a recombinant vaccine strain auxotrophic for D-alanine synthesis , comprising a mutation in a D-alanine racemase gene and in a D-amino acid transferase gene in the chromosome of said recombinant , wherein said further comprises a plasmid , wherein the plasmid comprises:a first nucleic acid sequence encoding a polypeptide, wherein said polypeptide comprises a heterologous antigen, and{'i': 'Listeria', 'a second nucleic acid sequence encoding a D-alanine racemase enzyme, wherein said plasmid does not confer antibiotic resistance upon said recombinant vaccine strain,'}{'i': Listeria', 'Listeria, 'whereby said D-alanine racemase gene complements said mutation in said chromosome of said recombinant , wherein said plasmid comprises a prfA gene, wherein said plasmid is stably maintained in said recombinant vaccine strain in the absence of an antibiotic selection, and wherein said first nucleic acid sequence is operably linked to a prokaryotic promoter/regulatory sequence, thereby inducing an immune response against a tumor or cancer in said subject.'}36. The method of claim 35 , wherein said polypeptide is a fusion protein comprising said heterologous antigen and an additional polypeptide claim 35 , wherein said additional polypeptide is a non-hemolytic fragment of an LLO protein claim 35 , a PEST-like amino acid sequence claim 35 , or an ActA protein or a fragment thereof.37. The method of claim 35 , wherein said second nucleic acid sequence is operably linked to said promoter/regulatory sequence.38. The method of claim 36 , wherein said heterologous antigen is an HPV E6 or E7.39. The method of claim 36 , wherein said heterologous antigen is PSA.40. ...

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25-08-2022 дата публикации

METHODS AND COMPOSITIONS FOR PRODUCING AN ADENOVIRUS VECTOR FOR USE WITH MULTIPLE VACCINATIONS

Номер: US20220265809A1
Принадлежит:

Methods for generating immune responses using adenovirus vectors that allow multiple vaccinations with the same adenovirus vector and vaccinations in individuals with preexisting immunity to adenovirus are provided. 136.-. (canceled)37. A composition comprising: a replication defective adenovirus vector comprising: a deletion in the E2b region; and a nucleic acid sequence encoding an antigen , wherein the antigen is a viral protein , and wherein the virus is a human immunodeficiency virus (HIV).38. The composition of claim 37 , wherein the replication defective adenovirus vector further comprises a deletion in the E1 region.39. The composition of claim 37 , wherein the nucleic acid sequence encoding the antigen is located in the E1 region.40. The composition of claim 37 , wherein the replication defective adenovirus vector further comprises a deletion in the E3 region.41. The composition of claim 37 , wherein the nucleic acid sequence encoding the antigen is located in the E3 region.42. The composition of claim 37 , wherein the replication defective adenovirus vector is derived from Adenovirus serotype 5.43. The composition of claim 37 , wherein the composition comprises the replication defective adenovirus vector at a concentration of at least 10virus particles/ml.44. The composition of claim 37 , wherein the replication defective adenovirus vector is not helper-adenovirus dependent.45. The composition of claim 37 , wherein the antigen is HIV gag protein.46. The composition of claim 37 , further comprising an adjuvant.47. The composition of claim 46 , wherein the adjuvant is granulocyte macrophage colony-stimulating factor (GM-CSF) claim 46 , granulocyte-colony stimulating factor (G-CSF) claim 46 , interferon-gamma (IFN-y) claim 46 , tumor necrosis factor-alpha (TNF-a) claim 46 , interleukin-2 (TL-2) claim 46 , IL-7 claim 46 , IL-12 claim 46 , IL-4 claim 46 , TL-5 claim 46 , IL-6 claim 46 , IL-10 claim 46 , IL-12 claim 46 , or a combination thereof.48. The ...

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25-08-2022 дата публикации

COMPOSITIONS AND METHODS FOR MAKING AND USING THERMOSTABLE IMMUNOGENIC FORMULATIONS WITH INCREASED COMPATIBILITY OF USE AS VACCINES AGAINST ONE OR MORE PATHOGENS

Номер: US20220265810A1
Принадлежит:

Embodiments of the present disclosure provide novel compositions, methods of use and methods for single composition, multi-dose, thermostable vaccine formulations. In certain embodiments, the present disclosure provides compositions and methods for dehydrating immunogenic agents in the presence of glass-forming agents, and coating the particles formed by the glass-forming agents. In other embodiments, the present disclosure provides for generating compositions for administering an immunogenic composition to a subject multiple times using a single immunogenic composition capable of time-release administration. In other embodiments, single-dose immunogenic agent-containing particles can be directed to two or more pathogens. In other embodiments, incompatible immunogenic agents against two or more different pathogens of immunogenic agent-containing particles disclosed herein can be mixed together and coated for timed-release administration to produce single-administration formulations capable of eliciting an immune response to the two or more pathogens in a subject. 1. An immunogenic agent-containing particle comprising:a central or innermost immunogenic agent-containing glassy microparticle comprising at least one immunogenic agent and at least one glass-forming agent; andone or more coating layers covering the central or innermost immunogenic agent-containing glassy microparticle.2. The immunogenic agent-containing particle according to claim 1 , wherein the central or innermost immunogenic agent-containing glassy microparticle further comprises at least one smoothing excipient.3. The immunogenic agent-containing particle according to claim 1 , wherein the at least one immunogenic agent comprises one or more antigens from a pathogenic virus claim 1 , a pathogenic bacteria claim 1 , a fungal pathogen; a peptide or polypeptide derived from a pathogenic virus claim 1 , a pathogenic bacteria or fungal pathogen; a recombinant molecule derived from a pathogenic virus claim ...

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25-04-2019 дата публикации

Immunogenic compositions comprising a papilloma viral capsid

Номер: US20190117760A1

The invention features immunogenic compositions and methods useful for eliciting an immune response. In preferred embodiments, papillomavirus or adenovirus vectors are used to elicit exceptionally potent antibody and T cells responses in disrupted epithelium. The methods are useful in preventing or treating a subject having a disease or an infection. In particular examples, the methods are useful for preventing or treating a viral infection.

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16-04-2020 дата публикации

CHIMERIC VIRUS-LIKE PARTICLES AND USES THEREOF AS ANTIGEN-SPECIFIC REDIRECTORS OF IMMUNE RESPONSES

Номер: US20200113996A1
Принадлежит:

This invention relates to chimeric virus-like particles (VLPs) assembled from a polypeptide comprising a papilloma p virus (PV) L1 protein or L1/L2 protein and a target peptide comprising a CD8+ T cell epitope derived from a human pathogen. This invention also relates to methods using the chimeric VLPs as antigen-specific redirectors of immune responses. 1. A chimeric virus-like particle (VLP) , comprising a papilloma virus (PV) L1 protein and a surface-displayed target peptide wherein the target peptide comprises a CD8+ T cell epitope of a human pathogen , wherein the CD8+ T cell epitope is not a tumor associated antigen , wherein the target peptide is conjugated to the VLP and wherein the target peptide is not conjugated to the VLP via a polyionic:cysteine sequence.2. The chimeric VLP of claim 1 , further comprising a PV L2 protein.3. The chimeric VLP of claim 1 , wherein the target peptide is conjugated to a cysteine claim 1 , lysine or arginine of the 1.1 protein via a disulfide linkage claim 1 , a maleimide linkage claim 1 , or an amide linkage.4. The chimeric VLP of claim 2 , wherein the target peptide is conjugated to a cysteine claim 2 , a lysine or an arginine of the L2 protein via a disulfide linkage claim 2 , a maleimide linkage claim 2 , or an amide linkage.5. The chimeric VLP of claim 1 , wherein the target peptide is not a peptide of a papilloma virus.6. The chimeric VLP of claim 1 , wherein the CD8+ T cell epitope is from an antigenic polypeptide of a childhood vaccine.7. The chimeric VLP of claim 1 , where in the pathogen is a virus claim 1 , a bacteria claim 1 , a fungus claim 1 , or a parasite.8. The chimeric VLP of claim 7 , where in the virus is a vaccinia virus claim 7 , varicella zoster virus claim 7 , a Herpes zoster virus claim 7 , rubella claim 7 , a hepatitis virus claim 7 , e.g. claim 7 , hepatitis A virus or hepatitis B virus or hepatitis C virus claim 7 , an influenza virus type A or type B claim 7 , a measles virus claim 7 , a mumps ...

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14-05-2015 дата публикации

Novel compositions and uses therefor

Номер: US20150132325A1
Автор: Ian Hector Frazer
Принадлежит: Admedus Vaccines Pty Ltd

The invention is directed to the use of (i) a first antigen corresponding to a target antigen of interest, together with (ii) a second antigen, corresponding to a modified form of the target antigen, whose rate of intracellular proteolytic degradation is increased, enhanced or otherwise elevated relative to the first antigen, in compositions and methods for inducing both humoral and cellular immunity in an individual. The ability to provide compositions, which are capable of inducing both host-protective antibody and cell-mediated immune responses, facilitates the generation of immunogenic compositions capable of combating, inter alia, conditions that have long latency periods and, therefore, benefit from the dual approach of prophylaxis and therapy in one delivery.

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02-05-2019 дата публикации

Improvement of L2 Peptide Immunogenicity

Номер: US20190125856A1
Принадлежит:

The present invention relates to an immunogenic polypeptide comprising a multitude of human papillomavirus (HPV) L2 N-terminal peptides corresponding to amino acids 20 to 50 of the L2 polypeptide of HPV16, wherein said HPV L2 N-terminal peptides are L2 N-terminal peptides from at least two different HPV genotypes. The present invention also relates to said immunogenic polypeptide for use in medicine and for use in vaccination against HPV infection. Moreover, the present invention relates to a polynucleotide encoding the immunogenic polypeptide and to a host cell comprising the same. Moreover, the present invention relates to kits, methods, and uses related to the immunogenic polypeptide of the invention. 1. An immunogenic polypeptide comprising a multitude of human papillomavirus (HPV) L2 N-terminal peptides corresponding to amino acids 20 to 50 of the L2 polypeptide of HPV16 , wherein said HPV L2 N-terminal peptides are L2 N-terminal peptides from at least four , different HPV genotypes; or are variants thereof comprising at most two amino acid substitutions per HPV L2 N-terminal peptide.2. The immunogenic polypeptide of claim 1 , wherein said multitude is a number of from 5 to 10.3. The immunogenic polypeptide of claim 1 , wherein said HPV L2 N-terminal peptides are peptides corresponding to amino acids 20 to 38 of the L2 polypeptide of HPV16.4. The immunogenic polypeptide of claim 1 , wherein said HPV L2 N-terminal peptides are L2 N-terminal peptides from at least five different HPV genotypes.5. The immunogenic polypeptide of claim 1 , wherein said immunogenic polypeptide comprises said HPV L2 N-terminal peptides in the sequence HPV 16-18-31-33-35-39-45-51-56-59-82.6. The immunogenic polypeptide of claim 1 , wherein said multitude HPV L2 N-terminal peptides comprises SEQ ID NO: 25 or 26 or is a variant of said immunogenic polypeptide comprising at most two amino acid substitutions per HPV L2 N-terminal peptide.7. The immunogenic polypeptide of claim 1 , further ...

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23-04-2020 дата публикации

COMPOSITIONS, METHODS AND USES FOR IMPROVED HUMAN PAPILLOMA VIRUS CONSTRUCTS

Номер: US20200121779A1
Принадлежит:

Embodiments of the present invention provide compositions and methods for recombinantly generating tagless constructs of proteins or peptides. In certain embodiments, recombinant proteins or peptides disclosed herein concern human papilloma virus (HPV). Other embodiments concern using these constructs in compositions to elicit immune responses in a subject to one or more HPV types. Therapeutic and prophylactic vaccines for the prevention and treatment of viral infections are also disclosed. Nucleic acids and expression vectors coding for constructs contemplated herein are provided. In certain embodiments, an HPV capsid protein generated is devoid of any fusion tags. In addition, truncated forms of HPV L1 are contemplated. 1. A bacterial plasmid construct comprising: 1) the nucleic acid represented by SEQ ID NO: 1;', '2) the nucleic acid represented by SEQ ID NO: 2;', '3) the nucleic acid represented by SEQ ID NO: 3;', '4) the nucleic acid represented by SEQ ID NO: 4;', '5) the nucleic acid represented by SEQ ID NO: 5;', '6) the nucleic acid represented by SEQ ID NO: 6;', '7) the nucleic acid represented by SEQ ID NO: 7; or', '8) the nucleic acid represented by SEQ ID NO: 8;, 'a target Human Papilloma Virus (HPV) DNA molecule comprising a transcription start codon, wherein the target HPV DNA molecule encodes one or more proteins or peptides, the HPV DNA molecule comprising one or more ofa promoter associated with the target HPV DNA molecule;a restriction site positioned between the promoter and the target HPV DNA molecule;a resistance gene capable of conferring resistance to a selection agent; andthe plasmid construct is devoid of any tag, or tracking agent, making the construct tagless.2. The bacterial plasmid construct of claim 1 , wherein the target HPV DNA molecule encodes a single protein or a chimeric protein.3. The bacterial plasmid construct of claim 1 , wherein the target HPV DNA molecule encodes one or more proteins or peptides of use in an immunogenic ...

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23-04-2020 дата публикации

Compositions and Methods of Treatment

Номер: US20200123571A1
Принадлежит: GLAXOSMITHKLINE BIOLOGICALS S.A.

The present invention relates to nucleic acid constructs capable of encoding antigenic peptides or polypeptides derived from multiple Human Papilloma Virus (HPV) early proteins, and to immunogenic compositions comprising such nucleic acid constructs and a pharmaceutically acceptable carrier. Such nucleic acid constructs and immunogenic compositions are useful in the treatment of persistent HPV infection and low-grade HPV lesions, particularly infections and lesions of human anogenital epithelial tissue, such as cervical epithelia. 2. The recombinant vector according to claim 1 , where said vector does not comprise any nucleic acid sequence encoding an antigenic polypeptide from an HPV Late 1 (L1) protein or an HPV Late 2 (L2) protein.3. The recombinant vector according to wherein the nucleic acid sequences express separate antigenic HPV polypeptides.4. The recombinant vector according to wherein the nucleic acid sequences express antigenic HPV polypeptides that are linked by a peptide linker.56.-. (canceled)7. The recombinant vector according to claim 1 , comprising antigenic polypeptide sequences selected from HPV types HPV16 claim 1 , HPV18 claim 1 , HPV31 claim 1 , HPV33 claim 1 , HPV35 claim 1 , HPV39 claim 1 , HPV45 claim 1 , HPV51 claim 1 , HPV52 claim 1 , HPV56 claim 1 , HPV58 claim 1 , HPV59 claim 1 , HPV68 claim 1 , HPV73 and HPV82.8. The recombinant vector according to claim 1 , wherein:(a) said first HPV early protein is Early 1 (E1), and said second HPV early protein is selected from Early 2 (E2), Early 6 (E6), and Early 7 (E7);(b) said first HPV early protein is E2, and said second HPV early protein is selected from E1, E6 and E7;(c) said first HPV early protein is E6, and said second HPV early protein is selected from E1, E2 and E7; or(d) said first HPV early protein is E7, and said second HPV early protein is selected from E1, E2 and E6.9. The recombinant vector according to claim 1 , wherein said first HPV early protein is Early 1 (E1) claim 1 , and ...

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03-06-2021 дата публикации

Detection of nucleic acids from multiple types of human papillomavirus

Номер: US20210164063A1
Принадлежит: Gen Probe Inc

Nucleic acid oligonucleotide sequences are disclosed which include amplification oligomers and probe oligomers which are useful for detecting multiple types of human papillomaviruses (HPV) associated with cervical cancer. Methods for detecting multiple HPV types in biological specimens by amplifying HPV nucleic acid sequences in vitro and detecting the amplified products are disclosed.

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09-05-2019 дата публикации

COMPOSITIONS, METHODS AND USES FOR THERMALLY STABLE MULTI-TARGETED ANTIGENS

Номер: US20190133954A1
Принадлежит:

Embodiments of the present invention provide for novel compositions and methods for making and using a thermally stable human papilloma virus (HPV) formulation or other stabilized multimeric virus formulation. Certain embodiments concern lyophilizing HPV formulations in the presence or absence of adjuvants. Other embodiments concern lypophilizing HPV capsomere vaccines in order to increase stability of an immunogenic composition against HPV infection for storage, delivery and use. In yet other embodiments, a single immunogenic composition can include a thermally stable formulation of multiple virus serotypes. Yet other embodiments disclosed herein concern multi-targeted antigen complexes lyophilized in formulations of use to prolong stability and/or enhance immunogenicity. Other embodiments concern exposing lyophilized multi-targeted antigen complexes to elevated temperatures to enhance immunogenicity of the antigens of the complex to multiple pathogens. 1. An immunogenic composition comprising:a broad-spectrum multi-targeted antigen construct;one or more non-reducing disaccharide agents;one or more volatile salts;wherein the immunogenic composition is essentially dried.2. The immunogenic composition according to claim 1 , wherein the one or more non-reducing disaccharide is selected from the group consisting of trehalose claim 1 , sucrose claim 1 , lactose claim 1 , or combinations thereof.3. The immunogenic composition according to claim 1 , wherein the one or more volatile salts comprise one or more of ammonium acetate claim 1 , ammonium formate claim 1 , ammonium carbonate claim 1 , ammonium bicarbonate claim 1 , triethylammonium acetate claim 1 , triethylammonium formate claim 1 , triethylammonium carbonate claim 1 , trimethylamine acetate trimethylamine formate claim 1 , trimethylamine carbonate claim 1 , pyridinal acetate and pyridinal formate claim 1 , or combinations thereof.4. The immunogenic composition according to claim 1 , wherein the composition is ...

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08-09-2022 дата публикации

Chimeric Papilloma Virus L1 Protein

Номер: US20220281925A1
Принадлежит:

The present invention relates to chimeric papilloma virus L1 proteins and polynucleotides encoding thereof, and also to HPV virus-like particles and the preparation methods thereof. Said chimeric papilloma virus L1 protein comprises an N-terminal fragment derived from L1 protein of the first papilloma virus type, said N-terminal fragment maintains the immunogenicity of the L1 protein of the corresponding type of HPV; and a C-terminal fragment derived from L1 protein of the second papilloma virus type, said L1 protein of the second papilloma virus type has a better expression level and a better solubility compared to the L1 proteins of other HPV types; wherein said chimeric papilloma virus L1 proteins have the immunogenicity of the L1 proteins of the corresponding HPV types. Said chimeric papilloma virus L proteins have better expression amount and solubility for mass production of vaccines. 1. A chimeric papilloma virus L1 protein comprising , from its N-terminus to C-terminus orientation ,(a) an N-terminal fragment derived from an L1 protein of a first papilloma virus type, said N-terminal fragment maintains an immunogenicity of the L1 protein of the first papilloma virus type; and(b) a C-terminal fragment derived from an L1 protein of a second papilloma virus type, said L1 protein of the second papilloma virus type has better expression level and solubility compared to the L1 proteins of other types,wherein said chimeric papilloma virus L1 protein has the immunogenicity of the L1 protein of the first papilloma virus type.2. The chimeric papilloma virus L1 protein according to claim 1 , wherein one of:said N-terminal fragment is a fragment obtained by truncating a C-terminus of a natural sequence of said L1 protein of the first papilloma virus type at any amino acid position within its α5 region, and a fragment having at least 98% identity therewith,said C-terminal fragment is a fragment obtained by truncating an N-terminus of the natural sequence of said L1 ...

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16-05-2019 дата публикации

HPV PARTICLES AND USES THEREOF

Номер: US20190142925A1
Принадлежит:

The invention relates to modified HPV particles that can be used therapeutically. Modified HPV particles may be used to deliver therapeutic agents, including siRNA molecules. Modified HPV particles may be used for the treatment of diseases or conditions of mucosal tissue, including HPV (human papilloma virus) infection and HPV-related tumors. 181.-. (canceled)82. A method comprising:expressing in a host cell nucleic acids encoding modified papillomavirus L1 proteins that comprise an FG loop corresponding to the amino acid sequence of SEQ ID NO: 66; andisolating nanoparticles self-assembled from the papillomavirus L1 proteins.83. The method of claim 82 , wherein the cell is selected from bacterial cells claim 82 , insect cells claim 82 , yeast cells claim 82 , and mammalian cells.84. The method of claim 83 , wherein the cell is a mammalian cell.85. The method of claim 84 , wherein the mammalian cell is a 293T cell.86. The method of claim 84 , wherein the mammalian cell is a 293FT cell.87. The method of claim 82 , wherein the modified papillomavirus L1 proteins are modified human papillomavirus L1 proteins.88. The method of claim 87 , wherein the modified papillomavirus L1 proteins are chimeric HPV16/31 L1 proteins.89. The method of claim 82 , wherein the nanoparticles comprise the papillomavirus L1 proteins and papillomavirus L2 proteins.90. A nanoparticle comprising a papillomavirus L1 protein comprising an FG loop comprising the amino acid sequence of SEQ ID NO: 66.91. The nanoparticle of claim 90 , wherein the nanoparticle comprises at least one heterologous compound.92. The nanoparticle of claim 91 , wherein the at least one heterologous compound comprises at least one therapeutic agent.93. The nanoparticle of claim 91 , wherein the at least one heterologous compound comprises at least one diagnostic agent.94. The nanoparticle of claim 90 , wherein the nanoparticle is a self-assembled nanoparticle.95. The nanoparticle of further comprising papillomavirus L2 ...

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31-05-2018 дата публикации

Next-Generation Sequencing-Based Genotyping Assay for Human Papilloma Virus (HPV)

Номер: US20180148780A1
Принадлежит:

Disclosed herein are compositions and methods for detecting and diagnosing HPV in subjects. The method includes using Next Gen Sequencing for detecting HPV in a sample and determining the specific subtype of HPV infection based on the sequencing data. 1. A method for detecting HPV nucleic acid in a biological sample of a subject suspected of having an HPV infection or an HPV associated disease , the method comprising: (a) isolating a nucleic acid sample from a biological sample obtained from the subject; (b) determining the nucleic acid sequence of the nucleic acid sample using a next generation (Next Gen) sequencing assay; and (c) determining the genotype of HPV in the sample ,wherein the method of determining the nucleic acid sequence of the nucleic acid sample comprises: (i) contacting the nucleic acid sample with at least one forward PCR primer, (ii) contacting the nucleic acid sample with at least one reverse PCR primer, (iii) amplifying the HPV nucleic acid using PCR, and (vi) sequencing the amplified nucleic acid products using a Next Gen Sequencer, andwherein the at least one forward PCR primer comprises a nucleic acid sequence selected from the group comprising SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8 and SEQ ID NO:9 and further comprises a nucleic acid sequence for use as a sequencing adaptor.2. (canceled)3. (canceled)4. The method of claim 1 , wherein the at least one forward PCR primer comprises at least two forward PCR primers claim 1 , wherein each of the at least two forward PCR primers comprises a nucleic acid sequence selected from the group comprising SEQ ID NO: 1 claim 1 , SEQ ID NO:2 claim 1 , SEQ ID NO:3 claim 1 , SEQ ID NO:4 claim 1 , SEQ ID NO:5 claim 1 , SEQ ID NO:6 claim 1 , SEQ ID NO:7 claim 1 , SEQ ID NO:8 and SEQ ID NO:9 and further wherein each of the at least two forward PCR primers further comprises a nucleic acid sequence for use as a sequencing adaptor.5. The method of ...

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01-06-2017 дата публикации

Vaccines For Human Papilloma Virus And Methods For Using The Same

Номер: US20170151320A1
Автор: Weiner David B., Yan Jian
Принадлежит:

Improved anti-HPV immunogens and nucleic acid molecules that encode them are disclosed. Immunogens disclosed include those having consensus HPV39 E6E7 and HPV45 E6E7. Pharmaceutical composition, recombinant vaccines comprising DNA plasmid and live attenuated vaccines are disclosed as well methods of inducing an immune response in an individual against HPV are disclosed. 1. A composition comprising at least one nucleotide sequence comprising an HPV E6-E7 fusion antigen selected from the group consisting of: HPV39 and HPV45.2. The composition of claim 1 , comprising one or more nucleotide sequences encoding an HPV E6-E7 fusion antigen selected from the group consisting of:a nucleotide sequence that encodes SEQ ID NO:25; nucleotide sequence that encodes SEQ ID NO:26;a nucleic acid sequence that is at least 95% homologous to a nucleic acid sequence nucleotide sequence that encodes SEQ ID NO:25; a nucleic acid sequence that is at least 95% homologous to a nucleotide sequence that encodes SEQ ID NO:26;a fragment of a nucleotide sequence that encodes SEQ ID NO:25; a fragment of a nucleotide sequence that encodes SEQ ID NO:26;a nucleic acid sequence that is at least 95% homologous to a fragment of a nucleotide sequence that encodes SEQ ID NO:25; and a nucleic acid sequence that is at least 95% homologous to a fragment of a nucleotide sequence that encodes SEQ ID NO:26.3. The composition of claim 2 , wherein the HPV E6-E7 fusion antigen has at least 98% homology with nucleotide sequences selected from the group consisting of:a nucleotide sequence that encodes SEQ ID NO:25 and a nucleotide sequence that encodes SEQ ID NO:26.4. The composition of claim 2 , wherein the HPV E6-E7 fusion antigen has at least 99% homology with nucleotide sequences selected from the group consisting of:a nucleotide sequence that encodes SEQ ID NO:25 and a nucleotide sequence that encodes SEQ ID NO:26.5. The composition of claim 2 , where the nucleotide sequences encoding the HPV E6-E7 fusion ...

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08-06-2017 дата публикации

MICRONEEDLE-BASED TRANSDERMAL DELIVERY SYSTEM AND METHOD OF MAKING SAME

Номер: US20170157036A1
Автор: DSOUZA Martin J.
Принадлежит:

A transdermal delivery system of microneedles containing a bioactive material, comprising at least one layer of a support material; at least one biodegradable needle associated with the support material, each needle comprising at least one biodegradable polymer and at least one sugar, wherein each biodegradable needle is hollow and is adapted to retain a bioactive material. 1. A transdermal delivery system , comprising:(a) at least one layer of a support material; i. at least one biodegradable polymer,', 'ii. at least one sugar;, '(b) at least one biodegradable needle associated with the support material, each needle comprising'}wherein each biodegradable needle is hollow and is adapted to retain a bioactive material.2. A method of forming transdeiiiial delivery system , comprising:(a) providing at least one biodegradable polymer material;(b) dissolving the polymer material in a solvent to form a solution;(c) mixing the solution of polymer material of step (b) with at least one sugar to form a polymer-sugar mixture;(d) providing a bioactive material;(e) providing a microneedle mold;(f) adding the bioactive material and the polymer-sugar mixture of step (c) to the microneedle mold; and,(g) forming at least one microneedle from the polymer-sugar mixture, the at least one microneedle having at least a portion that is hollow, wherein the bioactive material is retained within the hollow portion of the microneedle.3. The method of claim 2 , further comprising step (h) providing a support material and step (i) associating the at least one microneedle of step (g) with the support material.4. A biodegradable microneedle claim 2 , comprising: at least one biodegradable needle associated with the support material claim 2 , each needle comprising at least one biodegradable polymer claim 2 , and at least one sugar claim 2 , wherein each biodegradable needle is at least partially hollow and is adapted to retain a bioactive material.5. The system of claim 1 , wherein the ...

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07-06-2018 дата публикации

Assay system to identify HPV replication inhibitors in HT-screen

Номер: US20180155756A1
Принадлежит: ICOSAGEN CELL FACTORY OU

A U2OS-based model system using luciferase reporters to monitor the genome replication of alpha and beta HPVs is provided. A modified U2OS cell line is disclosed that expresses Firefly luciferase to measure toxicity of the screened compounds. In addition, provided are HPV18, HPV 16 and HPV5 marker genomes that express luciferase under the control of viral promoters used to measure changes in the viral copy number. This ready-to-use model system is capable of being used in high-throughput screens to identify compounds inhibiting initial amplification and stable maintenance as well as vegetative phase of various HPV subtypes. 1. An extrachromosomally maintainable plasmid for transfecting human osteosarcoma cell lines supporting all phases of HPV DNA replication , said plasmid comprising a complete or partial coding sequence of a marker gene inserted into the ORF of E2 protein whereby the expression of marker gene is regulated by the modulation of viral promoters.2Renilla. The plasmid of wherein the marker gene is luciferase having coding sequence of SEQ ID NO: 30.3. The plasmid of claim 1 , wherein the HPV is selected from alpha or beta group of HPV.4. The plasmid of claim 3 , wherein the HPV is HPV18 and the E2 ORF is according to SEQ ID NO: 14 or HPV is HPV 16 and the E2 ORF is according to SEQ ID NO: 34.5. The plasmid of claim 2 , wherein the HPV is HPV 5 and the E2 ORF is according to SEQ ID NO:15.6. The plasmid of claim 1 , wherein the plasmid has nucleic acid sequence SEQ ID NO: 1 claim 1 , SEQ ID NO: 3 or SEQ ID NO:42.7. A HPV18 marker genome according to SEQ ID NO: 4.8. A HPV 5 marker genome according to SEQ ID NO: 2.9. A HPV16 marker genome according to SEQ ID NO:43.10. A detectable fusion peptide comprising SEQ ID NO: 16 claim 1 , SEQ ID NO:17 or SEQ ID NO:35.11. A monoclonal human osteosarcoma cell line DSM ACC3258 enabling initial replication claim 1 , stable maintenance and vegetative amplificational replication of HPV DNA.12. The cell line of claim 11 , ...

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16-06-2016 дата публикации

FINE EPITOPE PEPTIDE CAPABLE OF INDUCING CROSS-REACTIVE ANTIBODIES AMONG HOMOLOGOUS PROTEINS IN HUMAN PAPILLOMA VIRUS E6 PROTEIN

Номер: US20160168206A1
Автор: Liu Riting, Xu Wanxiang
Принадлежит:

This invention relates to the minimal motif of an epitope on the E6 protein from human papilloma virus (HPV), and this minimal motif of the epitope induces a monoclonal antibody having cross-reactivity with some homologous proteins of HPVs. The inventors are the first to identify a fine antigenic epitope only existing conservatively on the E6 proteins of high risk HPV16, 33, 52 or 58). Therefore, the peptides comprising this epitope can be used to prepare immunogen or serological detection antigen against the HPV E6 proteins, or to prepare specific universal antibodies for a variety of high-risk/carcinogenic HPVs. 1. An isolated peptide , comprising the amino acid sequence of formula (I):{'br': None, 'EXRHY\u2003\u2003(I);'}wherein X represents the amino acid L or Y;and the peptide is derived from E6 proteins of human papilloma viruses (HPVs).2. The peptide described in claim 1 , comprising the amino acid sequence as shown in SEQ ID NO: 1 or SEQ ID NO: 2.3. The peptide described in claim 1 , wherein the peptide is derived from the E6 proteins of HPV18 claim 1 , HPV16 claim 1 , HPV52 claim 1 , HPV33 claim 1 , or HPV58.4. The peptide according to claim 1 , wherein the peptide is mixed with an adjuvant or coupled with a carrier protein for use as an immunogen against the E6 protein of HPVs.5. The peptide according to claim 4 , wherein the HPVs is HPV18 claim 4 , HPV16 claim 4 , HPV52 claim 4 , HPV33 claim 4 , or HPV58.6. A method for preparing an antibody that can bind specifically with an E6 protein of HPV18 claim 1 , HPV16 claim 1 , HPV52 claim 1 , HPV33 claim 1 , or HPV58 claim 1 , comprising immunizing with the peptide according to .7. A method for preparing a detection antigen for serological diagnosis of HPV 18 infection claim 1 , comprising coupling the peptide according to with another epitope to form a detection antigen with multiple epitopes.8. A method for diagnosing infection of HPV18 claim 1 , HPV16 claim 1 , HPV52 claim 1 , HPV33 claim 1 , or HPV58 claim ...

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14-06-2018 дата публикации

METHODS FOR POTENTIATING AN IMMUNE RESPONSE USING DEPOT-FORMING AND NON-DEPOT-FORMING VACCINES

Номер: US20180162913A1
Принадлежит: Immunovaccine Technologies Inc.

The present disclosure provides methods, vaccines and kits for potentiating an immune response to an antigen in a subject. The methods comprise administering to the subject at least one dose of a depot-forming vaccine comprising one or more antigens in a hydrophobic carrier; and subsequently administering to the subject at least one dose of a non-depot-forming vaccine comprising the one or more antigens. 1. A method for potentiating an immune response to an antigen in a subject , said method comprising:(i) administering to the subject at least one dose of a depot-forming vaccine comprising one or more antigens in a hydrophobic carrier; and(ii) subsequently administering to the subject at least one dose of a non-depot-forming vaccine comprising the one or more antigens.2. The method according to claim 1 , wherein:each of the at least one dose of the depot-forming vaccine is a priming dose that is capable of inducing an immune response to the one or more antigens; andeach of the at least one dose of the non-depot-forming vaccine is a maintenance or boosting dose that is capable of maintaining and/or boosting the immune response to the one or more antigens.3. (canceled)4. The method according to claim 2 , which comprises administering a first maintenance or boosting dose of the non-depot-forming vaccine within about 1 day claim 2 , 1 week claim 2 , 2 weeks claim 2 , 3 weeks claim 2 , 4 weeks claim 2 , 5 weeks claim 2 , 6 weeks claim 2 , 7 weeks claim 2 , 8 weeks claim 2 , 9 weeks or 10 weeks of a final priming dose of the depot-forming vaccine.5. (canceled)6. The method according to claim 1 , wherein the at least one dose of the depot-forming vaccine is one claim 1 , two claim 1 , three claim 1 , four or five doses.7. (canceled)8. The method according to claim 1 , wherein:the at least one dose of the non-depot-forming vaccine is one, two, three, four or five doses; orthe at least one dose of the non-depot-forming vaccine is a continuous repeated dosing once every day, ...

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23-06-2016 дата публикации

Compositions for mucusal delivery, useful for treating papillomavirus infections

Номер: US20160175426A1

Polypeptides, compositions, and methods for treatment of papillomavirus (PV) infections including a papillomavirus (PV) minor capsid (L2) polypeptide fragment and a cholera toxin B subunit (CTB) polypeptide are described. Polypeptides and compositions disclosed herein can be administered to the mucosa of a subject, resulting in unexpectedly beneficial production of cross-neutralizing antibodies.

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01-07-2021 дата публикации

Mutant of L1 Protein of Human Papillomavirus Type 39

Номер: US20210198322A1
Принадлежит:

The invention relates to a mutated HPV39 L1 protein (or a variant thereof), a sequence encoding the same, a method for preparing the same, and a virus-like particle comprising the same, wherein the protein (or a variant thereof) and the virus-like particle can induce the generation of neutralizing antibodies against at least two HPV types (e.g. HPV39 and HPV68, or HPV39, HPV68 and HPV70), and therefore can be used to prevent infection by said at least two HPV types, and a disease caused by said infection, such as cervical cancer and condyloma acuminatum. The invention further relates to the use of the protein and the virus-like particle in the manufacture of a pharmaceutical composition or a vaccine for preventing infection by said at least two HPV types, and a disease caused by said infection, such as cervical cancer and condyloma acuminatum. 1. A mutated HPV39 L1 protein or a variant thereof , wherein as compared with a wild type HPV39 L1 protein ,(I) the mutated HPV39 L1 protein has the following mutations:(1) N-terminal truncation of 1-25 amino acids; and(2) substitution of amino acid residues at positions 269-288 of the wild type HPV39 L1 protein with amino acid residues at the corresponding positions of a L1 protein of a second type of wild-type HPV;or,(II) the mutated HPV39 L1 protein has the mutations as defined in (1) and (2), and further has the following mutation:(3)(a) substitution of amino acid residues at positions 117-140 of the wild type HPV39 L1 protein with amino acid residues at the corresponding positions of a L1 protein of a third type of wild-type HPV; or(b) substitution of amino acid residues at positions 169-181 of the wild type HPV39 L1 protein with amino acid residues at the corresponding positions of a L1 protein of a third type of wild-type HPV; or(c) substitution of amino acid residues at positions 347-358 of the wild type HPV39 L1 protein with amino acid residues at the corresponding positions of a L1 protein of a third type of wild- ...

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01-07-2021 дата публикации

Methods of obtaining tumor-specific t cell receptors

Номер: US20210198341A1

Provided methods of obtaining a plurality of T cell receptors specifically recognizing a target tumor antigen peptide from an individual that has clinically benefitted from an immunotherapy, such as Multiple Antigen Specific Cell Therapy. Also provided tumor-specific TCRs, engineered immune cells expressing the TCRs and methods of treating a disease using the engineered immune cells.

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02-07-2015 дата публикации

CYAA-BASED CHIMERIC PROTEINS COMPRISING A HETEROLOGOUS POLYPEPTIDE AND THEIR USES IN THE INDUCTION OF IMMUNE RESPONSES

Номер: US20150184143A1
Принадлежит: GENTICEL

The invention relates to a chimeric protein comprising or consisting of from N-terminal to C-terminal, (a) a N-terminal part of a CyaA protein (b) a heterologous polypeptide, and (c) a C-terminal part of a CyaA protein. The invention also relates to a polynucleotide encoding a deleted version of a CyaA, as well as a polynucleotide encoding this chimeric protein. A composition comprising at least one chimeric protein(s) of the invention and the prophylactic and/or therapeutic uses of said composition are also part of the invention. 1. A polynucleotide encoding a CyaA-derived protein comprising or consisting of:{'i': 'Bordetella pertussis', '1) a fragment of the CyaA protein as set forth in SEQ ID NO: 2, the sequence of said fragment beginning with the first residue of SEQ ID NO:2 and ending with a residue located from position 183 to position 227 of SEQ ID NO:2 or a variant with at least 95% similarity with said fragment, fused to'}{'i': 'Bordetella pertussis', '2) a fragment of the CyaA protein as set forth in SEQ ID NO: 2, the sequence of said fragment beginning with a residue located from position 321 to position 387 of SEQ ID NO:2 and ending with the last residue of SEQ ID NO:2 or a variant with at least 95% similarity with said fragment.'}2. The polynucleotide according to claim 1 , wherein said CyaA-derived protein is selected from the group consisting of:1) a polypeptide comprising or consisting of the sequence as set forth in SEQ ID NO:10 or a variant with at least 95% similarity with this polypeptide;2) a polypeptide comprising or consisting of the sequence as set forth in SEQ ID NO:12 or a variant with at least 95% similarity with this polypeptide;3) a polypeptide comprising or consisting of the sequence as set forth in SEQ ID NO:19 or a variant with at least 95% similarity with this polypeptide;4) a polypeptide comprising or consisting of the sequence as set forth in SEQ ID NO:20 or a variant with at least 95% similarity with this polypeptide.3. The ...

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28-05-2020 дата публикации

DETECTION OF NUCLEIC ACIDS FROM MULTIPLE TYPES OF HUMAN PAPILLOMAVIRUS

Номер: US20200165689A1
Принадлежит:

Nucleic acid oligonucleotide sequences are disclosed which include amplification oligomers and probe oligomers which are useful for detecting multiple types of human papillomaviruses (HPV) associated with cervical cancer. Methods for detecting multiple HPV types in biological specimens by amplifying HPV nucleic acid sequences in vitro and detecting the amplified products are disclosed. 1. A detection reaction mixture comprising:at least one detection probe comprising (a) a target-specific sequence selected from the group consisting of SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:52, complements thereof, and RNA equivalents thereof; and (b) a detectable label that is joined directly or indirectly to the target-specific sequence of (a).2. The detection reaction mixture of claim 1 , wherein the detection reaction mixture further comprises a lithium salt selected from the group consisting of lithium succinate and lithium chloride.3. The detection reaction mixture of claim 2 , wherein the reaction mixture comprises both lithium succinate and lithium chloride.4. The detection reaction mixture of claim 1 , wherein the detection reaction mixture further comprises lithium lauryl sulfate.5. The detection reaction mixture of claim 4 , wherein the detection reaction mixture further comprises a lithium salt selected from the group consisting of lithium succinate and lithium chloride.6. The detection reaction mixture of claim 1 , wherein the detectable label is a chemiluminescent compound.7. The detection reaction mixture of claim 6 , wherein the chemiluminescent compound is an acridinium ester (AE) compound.8. An aqueous formulation comprising:(a) at least one detection probe oligomer comprising (i) a target-specific sequence selected from the group consisting of SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:52, complements thereof, and RNA equivalents thereof, and (ii) a detectable label that is joined ...

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28-06-2018 дата публикации

USE OF LIPOSOMES IN A CARRIER COMPRISING A CONTINUOUS HYDROPHOBIC PHASE AS A VEHICLE FOR CANCER TREATMENT

Номер: US20180177726A1
Принадлежит: Immunovaccine Technologies, Inc.

The invention compositions comprising a continuous hydrophobic phase and liposomes as a vehicle for delivery of an antigen capable of inducing a cytotoxic T lymphocyte (CTL) response and methods for their use in the treatment of cancer. 146.-. (canceled)47. A method for inducing an enhanced cytotoxic T lymphocyte (CTL) response thereby treating cancer or inhibiting or preventing the growth or proliferation of cancer cells in a subject in need of cancer treatment comprising administering to said subject a composition produced by a method comprising:encapsulating at least one antigen comprising a CTL epitope and at least one T helper epitopes in liposomes; andcombining said liposomes with a carrier consisting essentially of oil or which is a water-in-oil emulsion.48. The method of claim 47 , wherein the cancer is selected from the group consisting of: cervical claim 47 , vulvar claim 47 , melanoma claim 47 , breast claim 47 , lung claim 47 , ovarian claim 47 , multiple myeloma claim 47 , B cell lymphoma claim 47 , hepatoma claim 47 , sarcoma claim 47 , bladder claim 47 , prostate cancer claim 47 , thyroid claim 47 , H/N tumors claim 47 , colon claim 47 , rectal claim 47 , renal claim 47 , pancreatic claim 47 , gastric claim 47 , adenocarcinoma claim 47 , T cell leukemia claim 47 , lymphosarcoma claim 47 , uterine claim 47 , esophageal claim 47 , non-Hodgkin's lymphomas claim 47 , endometrial claim 47 , and RCC tumors.49. The method of claim 47 , wherein said T helper epitope is a separate molecule from said antigen.50. The method of claim 47 , wherein said antigen comprises said T helper epitope or wherein said antigen is fused to said T helper epitope.51. The method of claim 47 , wherein said antigen comprises a combination of CTL epitopes.52. The method of claim 47 , wherein said CTL epitope is derived from a tumor-associated protein.53. The method of claim 47 , wherein said CTL epitope is derived from a virus.54. The method of claim 47 , wherein said liposomes are ...

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28-06-2018 дата публикации

Hpv vaccines

Номер: US20180179257A1
Принадлежит: Hookipa Biotech GmbH

Provided herein are genetically modified arenaviruses suitable as vaccines against neoplastic diseases or cancer. The invention also relates to pharmaceutical compositions and methods for the prevention or treatment of certain infections causing neoplastic diseases or cancer, such as infections with oncogenic viruses. Specifically, provided herein are pharmaceutical compositions, vaccines, and methods of preventing or treating diseases and conditions caused by and associated with infections with Human Papillomavirus (HPV), such as cervical cancer, anogenital cancer, head and neck cancer and skin cancers. Also provided herein are immunotherapies for the treatment of a neoplastic disease, such as a neoplastic disease caused by infection with oncogenic viruses.

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07-07-2016 дата публикации

RECOMBINANT VIRUS-LIKE PARTICLES ENCODED BY MULTI-GENE VECTOR

Номер: US20160194662A1
Принадлежит:

The invention describes novel virus-like particles for use as vaccines, diagnostic tools and R&D tools based on recombinant DNA and cell cultivation techniques for production. The recombinant virus-like particles of the invention are assembled by polypeptide chains that incorporate several, in particular two or more, different epitopes which are selected either (a) from different viral strains of the same virus and/or (b) from different serotypes of the same virus and/or (c) from different viral strains specific for different hosts. These epitopes are then displayed on the particle surface. 116-. (canceled)17. A single baculoviral vector encoding a recombinant virus-like particle comprising(i) two or more polynucleotides coding for different epitopes or different proteins comprising epitopes which are selected either (a) from different viral strains of the same virus and/or (b) from different serotypes of the same virus and/or (c) from different viral strains specific for different hosts;(ii) polynucleotides coding for proteins forming a complete virus-like surface; and(iii) polynucleotides coding for capsid and/or nucleopore proteins.18. The baculoviral vector according to comprising three or more different epitopes or different proteins comprising epitopes.19. The baculoviral vector according to comprising four or more different epitopes or different proteins comprising epitopes.20. The baculoviral vector according to comprising six claim 17 , nine or twelve epitopes or different proteins comprising epitopes.21. The baculoviral vector according to wherein the epitopes are from three or more different virus strains or serotypes.22. The baculoviral vector according to further comprising B- and/or T-cell epitopes.23. The baculoviral vector according to further comprising fluorescent proteins claim 17 , proteins useful for purification purposes of the particles or for attaching a label claim 17 , and/or proteinaceous structures required for transport processes.24. The ...

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20-06-2019 дата публикации

Compositions, methods and uses for thermally stable human papillomavirus formulations

Номер: US20190184001A1
Принадлежит: University of Colorado

Embodiments of the present invention provide for novel compositions and methods for making and using a thermally stable human papilloma virus (HPV) formulation or other stabilized multimeric virus formulation. Certain embodiments concern lyophilizing HPV formulations in the presence or absence of adjuvants. Other embodiments concern lypophilizing HPV capsomere vaccines in order to increase stability of an immunogenic composition against HPV infection for storage, delivery and use. In yet other embodiments, a single immunogenic composition can include a thermally stable formulation of multiple virus serotypes.

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20-06-2019 дата публикации

HPV EPITOPES TARGETED BY T CELLS INFILTRATING CERVICAL MALIGNANCIES FOR USE IN VACCINES

Номер: US20190184002A1

The present invention relates to novel CD4+ and CD8+ T cell epitopes that are specific for HPV-specific E6 and E7 oncoproteins, to peptides comprising these novel T cell epitopes, and to (vaccine) compositions comprising these peptides for use in methods for the prevention and/or treatment of HPV related diseases. Preferred epitopes are recognized by a T cell that infiltrates a cervical neoplastic lesion or by a T cell from a draining lymph node, and are presented by an HLA-DQ or HLA-DP molecule, or an HLA-B. 1. An immunogenic pharmaceutical composition comprising:(a) a peptide having a length of no more than 90 amino acids and comprising at least 31 contiguous amino acids from the amino acid sequence of an HPV E7 protein, wherein the contiguous amino acid sequence comprises SEQ ID NO:17; and(b) an immune-stimulating amount of a pharmaceutically acceptable adjuvant.2. The immunogenic pharmaceutical composition according to claim 1 , wherein the length of the contiguous amino acid sequence is 33-35 amino acids.3. The immunogenic pharmaceutical composition according to claim 1 , wherein the contiguous amino acid sequence comprises an epitope that is presented by an HLA-B molecule claim 1 , preferably wherein the HLA-B molecule is an HLA-B7 claim 1 , HLA-B14 claim 1 , HLA-B27 or HLA-B57 molecule.4. The immunogenic pharmaceutical composition according to claim 1 , wherein the peptide comprises or consists of HPV16 E7 64-98.5. The immunogenic pharmaceutical composition according to claim 1 , wherein the composition comprises at least two different peptides as defined in any one of -.6. The immunogenic pharmaceutical composition according to claim 1 , wherein the pharmaceutically acceptable adjuvant acts via a Toll-like receptor.7. The immunogenic pharmaceutical composition according to claim 1 , wherein the composition is for intravenous claim 1 , subcutaneous claim 1 , intramuscular claim 1 , mucosal claim 1 , intradermal and/or intracutaneous administration.8. The ...

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14-07-2016 дата публикации

PAPILLOMAVIRUS-LIKE PARTICLES (VLP) AS BROAD SPECTRUM HUMAN PAPILLOMAVIRUS (HPV) VACCINES

Номер: US20160200774A1
Принадлежит:

This invention relates, e.g., to a virus-like particle (VLP) composition assembled from a chimeric polypeptide comprising a papilloma virus (e.g., human papillomavirus, or HPV) L1 major capsid protein, into which is inserted a surface-displayed peptide comprising a neutralizing epitope of a papillomavirus L2 protein. Vaccine compositions comprising the VLP are described, as well as methods for inducing an immune response (e.g., vaccinating) a subject against papilloma virus, using the VLP, and kits comprising the VLP, for carrying out a method of the invention. 1. A virus-like particle (VLP) composition , assembled from a chimeric polypeptide comprising a papilloma virus (PV) L1 protein into which is inserted a surface-displayed peptide consisting of the following sequence from a papillomavirus L2 protein:a) (D/Q/H/E)(L/I)Y(K/P/R/Q/S)(T/S/A/G)CK(Q/I/V/L/A)(A/S/T)(G/N)(T/N)CPPD (W)(I/V/Q)(P/N/D)(K/R)(V/I/L) (SEQ ID NO:1), orb) abYcdCKefghCPPDijklm (SEQ ID NO:2), where a=(D/Q/H/E); b=(L/I); c=(K/P/R/Q/S); d=(T/S/A/G); e=(Q/I/V/L/A); f=(A/S/T); g=(G/N); h=(T/N); i=(I/V); j=(I/V/Q); k=(P/N/D); l=(K/R); m=(V/I/L), orc) a sequence that is at least 80, 85, 90 or 95% identical to SEQ ID NO: 1 or SEQ ID NO:2.2. The VLP of claim 1 , wherein the inserted L2 peptide is one of the peptides listed in or in Table 1.3. The VLP of claim 1 , wherein the inserted L2 peptide is from the HPV 16 L2 protein claim 1 , and has the amino acid sequence QLYKTCKQAGTCPPDIIPKV (SEQ ID NO:9).4. The VLP of claim 1 , wherein the inserted L2 peptide is at least 80 claim 1 , 85 claim 1 , 90 or 95% identical to SEQ ID NO:9.5. The VLP of claim 1 , wherein the inserted L2 peptide is from the HPV18 L2 protein claim 1 , and has the amino acid sequence DLYKTCKQSGTCPPD VVPKV (SEQ ID NO: 10).6. The VLP of claim 1 , wherein the inserted L2 peptide is from BPV1/2 L2 protein claim 1 , and has the amino acid sequence DLYRTCKQAGTCPPDVIPKV (SEQ ID NO:22).7. The VLP of claim 1 , wherein the L2 peptide is inserted ...

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14-07-2016 дата публикации

Truncated L1 Protein of Human Papillomavirus Type 58

Номер: US20160200776A1
Принадлежит:

Provided are an N-terminal truncated L1 protein of the Human Papillomavirus Type 58, a coding sequence and preparation method thereof, and a virus-like particle comprising the protein. Uses of the protein and the virus-like particle in the preparation of a pharmaceutical composition or a vaccine are further provided. The pharmaceutical composition or vaccine is used for prevention of HPV infection and a disease caused by HPV infection. 1. A truncated HPV58 L1 protein , wherein said truncated HPV58 L1 protein has a truncation at exactly amino acids 2-5 , 2-15 , 2-35 , 2-40 , 2-60 or 2-70 , only , at its N-terminal , as compared with wild type HPV58 L1 protein.2. The truncated HPV58 L1 protein according to claim 1 , wherein said truncated HPV58 L1 protein has an amino acid sequence as set forth in SEQ ID NO:1 claim 1 , SEQ ID NO:2 claim 1 , SEQ ID NO:3 claim 1 , SEQ ID NO:5 claim 1 , SEQ ID NO:6 claim 1 , or SEQ ID NO:7.3. The truncated HPV58 L1 protein according to claim 1 , wherein said truncated HPV58 L1 protein has an amino acid sequence as set forth in SEQ ID NO:1.4. An isolated nucleic acid claim 1 , encoding the truncated HPV58 L1 protein according to .5. A vector comprising the isolated nucleic acid according to .6. A host cell claim 4 , wherein said host cell comprises the isolated nucleic acid according to or a vector comprising the isolated nucleic acid.7. A HPV58 virus-like particle claim 1 , comprising or consisting of the truncated HPV58 L1 protein according to .8. A pharmaceutical composition or vaccine comprising the HPV58 virus-like particle according to claim 7 , and optionally comprising pharmaceutically acceptable carriers and/or excipients.9. The pharmaceutical composition or vaccine according to claim 8 , wherein the HPV58 virus-like particle is present at an amount effective for preventing HPV infection or cervical cancer.10. A method of preventing HPV infection or a disease caused by HPV infection claim 7 , comprising administering to a subject ...

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