METHOD OF PROTECTING AGAINST STAPHYLOCOCCAL INFECTION

... ²²²A method of preventing or treating staphylococcal bacterial infection in an ²individual is disclosed. A vaccine based on a conjugate the 336 polysaccharide ²antigen can be used for active protection in individuals who are to be ²subjected to conditions that place them at immediate risk of developing a ²bacterial infection, as would be case in the context of a catheterization or a ²surgical procedure. Alternatively, antibodies raised in response to the ²antigen can be used to treat or to provide passive protection to individuals. ²The method can be used in a population of patients at risk for infection by ²various species of Staphylococcus or various types of Staphylococcus aureus.² ...

ADJUVANT COMPOSITIONS COMPRISING A NON-IONIC ISOTONICITY AGENT

Adjuvant and immunogenic compositions comprising a TLR-4 agonist and a saponin in a liposomal formulation, and a non-ionic isotonicity agent are provided, wherein the concentration of sodium chloride or ionic strength is less than 100mM.

VACCINE

... ²²²This invention relates to HIV polypeptide and polynucleotide fusions of Gag, ²Pol and Nef which are useful in immunogenic compositions and vaccines. The ²invention relates in particular to a polypeptide which comprises Nef or an ²immunogenic fragment thereof, and p17 Gag and/or p24 Gag or immunogenic ²fragments thereof, wherein when both p17 and p24 Gag are present there is at ²least one HIV antigen or immunogenic fragment between them. The polypeptide ²may also comprise Pol or RT or an immunogenic fragment thereof.² ...

VACCINE

... ²²²The present invention relates to a combination of 2 or more S pneumoniae ²proteins, their manufacture and use in medicine as a vaccine. Such ²combinations are particularly useful for the protection of infants and elderly ²against streptococcal infection.² ...

USE OF ALPHA-TOXIN FOR TREATING AND PREVENTING STAPHYLOCOCCUS INFECTIONS

Compositions and vaccines comprising an S. aureus alpha-toxin antigen and a pharmaceutically acceptable carrier are provided, and are useful for treating and preventing infections. The S. aureus alpha-toxin antigen may contain at least two alterations that reduce its toxicity and/or may be conjugated to or co-administered with another bacterial antigen. Specifically, compositions and vaccines comprising (i) a S. aureus alpha-toxin antigen and (ii) one or more additional bacterial antigens other than said S. aureus alpha-toxin antigen wherein at least one of said one or more additional bacterial antigens is an additional Staphylococcal antigen selected from the group consisting of S. aureus Type 5, S. aureus Type 8, and combinations thereof are provided. The compositions and vaccines may further comprise one or more further bacterial antigens selected from the group consisting of S. aureus 336, staphylococcal leukocidin antigens, and microbial surface components recognizing adhesive matrix ...

VACCINE

The present invention discloses an immunogenic composition comprising S. pneumoniae capsular saccharide conjugates from serotypes 19A and 19F wherein 19A is conjugated to a first bacterial toxoid and 19F is conjugated to a second bacterial toxoid. Vaccines, methods of making vaccines and uses of the vaccines are also described.

CONJUGATION OF ANITIGEN TO CARRIER PROTEIN USING TRIACETOXYBOROHYDRIDE

The present invention process a process for conjugation of an antigen comprising the steps of a) activating the antigen to form an activated antigen; b) reacting the activated antigen and a carrier protein or a linker to form an imine group linking the activated antigen to the carrier protein or the linker; and c) reducing the imine group using a reducing agent comprising a triacetoxyborohydride moeity to form a conjugated antigen or an antigen-linker; and optionally d) reacting the antigen linker with a carrier protein to form a conjugated antigen; optionally wherein the antigen originates from Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Enterococcus faecium, Enterococcus faecalis, Salmonella Vi, or Staphylococcus epidermidis, optionally further comprising a step a') of lyophilising the activated antigen and a carrier protein followed by reconstitution in DMSO or DMF.

PSEUDOMONAS ANTIGENS AND ANTIGEN COMBINATIONS

CONJUGATED VI SACCHARIDES

REGIMENS FOR IMMUNISATION WITH MENINGOCOCCAL CONJUGATES

METHODS FOR MAKING SACCHARIDE-PROTEIN GLYCOCONJUGATES

CASB618 Polynucleotides and Polypeptides and Their Use

CASB618 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing CASB618 polypeptides and polynucleotides in diagnostics, and vaccines for prophylactic and therapeutic treatment of cancers, particularly ovarian and colon cancers, autoimmune diseases, and related conditions.

Polysaccharide immunogens conjugated to E. coli carrier proteins

E. coli proteins have been identified that are useful as carrier proteins to improve a response to a polysaccharide immunogen conjugated to such protein. In particular, AcfD precursor protein (orf3526 polypeptide), Flu antigen 43 protein (orf1364 polypeptide), and Sel1 repeat-containing protein (upec-5211 polypeptide) have been shown to be effective. Additionally, these E. coli proteins can enhance the immune response to glucans, particularly fungal glucans.

Fusion proteins and combination vaccines comprising Haemophilus influenzae Protein E and Pilin A

There is provided a method of treating chronic hepatitis B infection (CHB) in a human, comprising the steps of: a) administering to the human a composition comprising a replication-defective chimpanzee adenoviral (ChAd) vector comprising a polynucleotide encoding a hepatitis B surface antigen (HBs) and a nucleic acid encoding a hepatitis B virus core antigen (HBc); b) administering to the human a composition comprising a Modified Vaccinia Virus Ankara (MVA) vector comprising a polynucleotide encoding a hepatitis B surface antigen (HBs) and a nucleic acid encoding a hepatitis B virus core antigen (HBc); and c) administering to the human a composition comprising a recombinant hepatitis B surface antigen (HBs), recombinant hepatitis B virus core antigen (HBc) and an adjuvant.

Vaccines

The invention relates to use of an antigen derived from the circumsporozoite protein (CS) protein of Plasmodium falciparum which is expressed at the pre-erythrocytic stage of malarial infection in combination with a pharmaceutically acceptable adjuvant, in the manufacture of a medicament for vaccinating infants against malaria.

Methods of boosting immune responses

The present invention relates to immunogenic compositions, such as vaccines, comprising immunogenic polypeptides from Haemophilus influenzae and Moraxella catarrhalis, for use in methods of boosting an immune response and methods of treatment using same. More particularly, the invention relates to use of such immunogenic compositions in methods of treating or preventing exacerbation of chronic obstructive pulmonary disease.

IMMUNOGENIC COMPOSITION

The present invention discloses modified Staphylococcus aureus HIa proteins which show reduced tendency to aggregate, improving protein stability and yield. Said modified HIa proteins optionally also contain glycosylation site consensus sequences. The invention also discloses a conjugate comprising a modified HIa protein and an antigen (for example a Staphylococcus aureus saccharide antigen), wherein the antigen is linked to an amino acid residue of the modified HIa protein.

Epstein-barr virus antigen constructs

The invention provides Epstein-Barr Virus antigen polynucleotides, polypeptides and vectors; as well as immunogenic compositions comprising the same. It includes the use of Epstein-Barr Virus antigen constructs to produce vaccines for treating and preventing Epstein-Barr Virus infections and Epstein-Barr Virus-associated diseases, such as multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus.

THE TUBERCULOSIS RV2386C PROTEIN, COMPOSITIONS AND USES THEREOF

The present invention is directed to a polypeptide which comprises: (i) an Rv2386c protein sequence; (ii) a variant of an Rv2386c protein sequence; or (iii) an immunogenic fragment of an Rv2386c protein sequence. In other aspects the invention is directed to associated polynucleotides, fusion proteins and methods for the treatment or prevention of tuberculosis.

LIPOSOME PRODUCTION USING ISOPROPANOL

The present invention provides methods for producing a lipidic film comprising the steps of: (i) dissolving a lipid mix in isopropanol to form a homogeneous mix; and (ii) removing the isopropanol from the homogeneous mix to form a lipidic film, wherein the lipid mix comprises a lipid and cholesterol.

PROCESS FOR PRODUCING INFLUENZA VACCINE

A process for producing a split influenza virus preparation or subunit influenza preparation comprising the steps of: (i) providing a whole virus preparation; (ii) splitting the whole virus preparation in the presence of a first detergent; (iii) adding t-octylphenoxypolyethoxyethanol (TRITON X-100™) to the resulting split virus preparation; and (iv) filtering the split virus preparation.

Meningococcal fHBP polypeptides

... fHBP is a protein in Neisseria meningitidis. Three families of fHBP are known. To increase the ability of a fHBP protein to elicit antibodies that are cross-reactive between the families, fHBP is selected or engineered to have a sequence which can elicit broad-spectrum bactericidal anti-meningococcal antibodies after administration to a host animal.

NOVEL METHODS FOR INDUCING AN IMMUNE RESPONSE

The present invention relates to methods for inducing an immune response, in particular methods for inducing an immune response against mycobacterial infections or disease comprising (i) at least one administration of a polypeptide Rv1196 related antigen and at least one administration of an adenovirus encoding a Rv1196 related antigen or (ii) at least one administration of a polypeptide Rv0125 related antigen and at least one administration of an adenovirus encoding a Rv0125 related antigen. Associated compositions, adenoviral constructs and polynucleotide sequences are also provided.

USPA2 PROTEIN CONSTRUCTS AND USES THEREOF

The present invention relates to compositions comprising Moraxella catarrhalis (M. catarrhalis) Ubiquitous surface protein A2 (UspA2). More particularly, the present application relates to UspA2 protein constructs and immunogenic compositions comprising the constructs, vaccines comprising such immunogenic compositions and therapeutic uses of the same. The invention further relates to compositions comprising UspA2 in combination with at least one antigen from Haemophilus influenzae, immunogenic compositions comprising the antigens, vaccines comprising such immunogenic compositions and therapeutic uses of the same.

Adjuvanted influenza virus compositions

The present invention relates to influenza vaccine formulations and vaccination regimes for immunising against influenza disease, their use in medicine, in particular their use in augmenting immune responses to various antigens, and to methods of preparation. In particular, the invention relates to multivalent influenza immunogenic compositions comprising an influenza antigen or antigenic preparation thereof from at least two influenza virus strains, at least one strain being associated with a pandemic outbreak or having the potential to be associated with a pandemic outbreak, in combination with an oil-in-water emulsion adjuvant.

Meningococcal fHBP polypeptides

... fHBP is a protein in Neisseria meningitidis. Three families of fHBP are known. To increase the ability of a fHBP protein to elicit antibodies that are cross-reactive between the families, fHBP is selected or engineered to have a sequence which can elicit broad-spectrum bactericidal anti-meningococcal antibodies after administration to a host animal.

PRAME PURIFICATION

Methods and processes for the purification of PRAME are provided. In particular, methods for reducing the aggregation of PRAME during a diluent exchange from diluent A to diluent B comprising: (i) adding a polyanionic compound to diluent A prior to or contemporaneously with the exchange; and (ii) exchanging protein from diluent A to diluent B are provided. Compositions produced by the method are also provided. 128-. (canceled)29. A method for reducing the aggregation of a protein during a diluent exchange from diluent A to diluent B comprising:(i) adding a polyanionic compound to diluent A prior to or contemporaneously with the exchange; and(ii) exchanging protein from diluent A to diluent B, wherein the protein is PRAME.30. The method according to claim 29 , wherein the polyanionic compound is added prior to the diluent exchange.31. The method or use according to claim 29 , wherein diluent A comprises a detergent.32. The method according to claim 31 , wherein the detergent is an anionic detergent.33. The method according to claim 32 , wherein the detergent is selected from the group consisting of: SDS claim 32 , sodium docusate and lauryl sarcosyl.34. The method of claim 29 , wherein diluent B is substantially free of detergent.35. The method of claim 29 , wherein diluent B comprises 5.0 mM borate claim 29 , sucrose 3.15% w/v at pH 9.8.36. The method of claim 29 , wherein the protein comprises a His-tag.37. The method of claim 29 , wherein the polyanionic compound has a net negative charge of at least 8.38. The method of claim 29 , wherein the polyanionic compound is an oligonucleotide.39. The method of claim 38 , wherein the oligonucleotide is 5 to 200 nucleotides in length.40. The method of claim 39 , wherein the oligonucleotide comprises a CpG.42. The method of claim 41 , wherein the diluent exchange is achieved by dialysis or diafiltration.43. The method of claim 42 , wherein the method further comprises step (iii) formulating the protein into diluent C.44. The ...

Immunization of large mammals with low doses of RNA

RNA encoding an immunogen is delivered to a large mammal at a dose of between 2 μg and 100 μg. Thus, the invention provides a method of raising an immune response in a large mammal, comprising administering to the mammal a dose of between 2 μg and 100 μg of immunogen-encoding RNA. Similarly, RNA encoding an immunogen can be delivered to a large mammal at a dose of 3 ng/kg to 150 ng/kg. The delivered RNA can elicit an immune response in the large mammal.

IMMUNOGENIC COMPOSITION COMPRISING CLOSTRIDIUM DIFFICILE TOXIN A AND TOXIN B FUSION PROTEIN

CA 02837395 2015-11-05 ABSTRACT The present invention relates to fusion proteins comprising fragments from toxin A and/or toxin B of Clostridium difficile, in particular the invention relates to proteins comprising a first fragment and a second fragment, wherein the first fragment is a toxin A repeating domain fragment; (ii) the second fragment is a toxin B repeating domain fragment; (iii) the first fragment has a first proximal end; (iv) the second fragment has a second proximal end; and wherein the first fragment and the second fragment are adjacent to one another and wherein the polypeptide elicits antibodies that neutralize toxin A or toxin B or both. The invention further relates to compositions comprising fragments or variants of SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33 or SEQ ID NO:34 or SEQ ID NO:35.

IMMUNOGENIC COMPOSITION

IMMUNOGENIC COMPOSITIONS

MODIFIED SACCHARIDES

IMMUNISATION OF LARGE MAMMALS WITH LOW DOSES OF RNA

RSV IMMUNIZATION REGIMEN

Immunogenic composition

The present invention relates to immunogenic compositions comprising a Clostridium difficile (C. difficile) polypeptide and an aluminum-free adjuvant.

Immunogenic proteins and compositions

The invention provides proteins and compositions for the treatment and prevention of Streptococcus agalactiae (Group B streptococcus; GBS).

Integration of meningococcal conjugate vaccination

Conjugated meningococcal capsular saccharides will be introduced into immunization schedules in the near future, but the phenomenon of “carrier suppression” must first be addressed, particularly where multiple conjugates are to be used. It has been found that diphtheria toxoid and its derivatives (such as CRM197) can safely be used as the carrier protein, even where multiple meningococcal conjugates are administered at the same time and where a patient has previously been exposed to the carrier protein, either in the form of a previous immunogen (e.g. in a DTP vaccine) or as a previous carrier protein (e.g. in a Hib or pneumococcal conjugate vaccine). The invention provides a method for immunizing a patient, comprising administering multiple conjugates of meningococcal capsular saccharides, wherein each conjugate comprises a diphtheria toxoid (or derivative thereof) carrier protein, and the capsular saccharide, and wherein the patient has been pre-immunized with a diphtheria toxoid (or ...

Escherichia coli immunogens with improved solubility

Variants of the pathogenic E. coli AcfD precursor have been identified with increased solubility as compared to the native AcfD protein that raise a substantially similar immune response in a subject as the native AcfD protein.

PURIFICATION OF SECRETED POLYSACCHARIDES FROM S. AGALACTIAE

The invention relates to bacterial mutants, particularly from , that secrete capsular polysaccharide and methods of purifying the secreted bacterial capsular polysaccharides from culture medium. The extracted polysaccharides are useful for producing vaccines comprising the polysaccharides alone or conjugated to proteins. 1Streptococcus agalactiaeStreptococcus agalactiae. A method for producing a capsular polysaccharide from comprising: culturing in a suitable culture medium a strain comprising a CpsA or CpsD mutant that exhibits increased secretion of capsular polysaccharide compared to secretion by the wild-type strain , and recovering the capsular polysaccharide from the culture medium.2Streptococcus agalactiae. The method of wherein the strain comprises a mutant CpsA nucleotide sequence selected from:(a) a truncated CpsA nucleotide sequence;(b) a CpsA nucleotide sequence where the LytR domain of SEQ ID NO:40, the LytR domain of SEQ ID NO:3 or the PFAM domain of SEQ ID NO:41 is deleted;(c) a CpsA nucleotide sequence having an alteration resulting in a substitution of at least one amino acid residue selected from the group consisting of: R271, R366, D375, R378 and Q382 numbered according to CpsA protein (SEQ ID NO: 2); and(d) a CpsA nucleotide sequence having an alteration resulting in a substitution of at least one amino acid residue selected from the group consisting of: D238, R248, D250, R271 and R368 numbered according to CpsA protein (SEQ ID NO: 2).3Streptococcus agalactiae. The method of wherein the strain comprises a mutant CpsD nucleotide sequence selected from:{'i': 'Streptococcus agalactiae;', '(a) deletion of the nucleotide sequence that encodes SEQ ID NO:13 in wild-type'}(b) a CpsD nucleotide sequence having an alteration resulting in a substitution of at least one amino acid residue selected from the group consisting of K49, S50, D73 and P154 numbered according to SEQ ID NO:11; and(c) SEQ ID NO:16.4Streptococcus agalactiaeStreptococcus agalactiae. The ...

METHOD OF TREATMENT

A method of immunising a human female subject to decrease the risk of Group B Streptococcus (GBS) disease in an infant born to the subject, by providing a priming dose of a GBS vaccine and, more than thirty days after the priming dose, providing a boosting dose of a GBS vaccine.

Vaccine comprising an oil in water emulsion

The present invention provides an immunogenic composition comprising an antigen or antigen composition and an adjuvant composition comprising an oil in water emulsion, wherein said oil in water emulsion comprises 0.5-10 mg metabolizable oil, 0.5-11 mg tocol and 0.1-4 mg emulsifying agent, per human dose.

NOVEL COMPOSITION

The present invention provides a human dose of an immunogenic composition comprising an antigen or antigenic preparation, in combination with an adjuvant which adjuvant comprises an immunologically active saponin fraction derived from the bark of Quillaja Saponaria Molina presented in the form of a liposome and a lipopolysaccharide wherein said saponin fraction and said lipopolysaccharide are both present in said human dose at a level of below 30~g. The present invention further provides an adjuvant composition in a human dose suitable volume comprising between 1 and 30 ~g of a lipopolysaccharide and between 1 and 30 ~g of an immunologically active saponin fraction presented in the form of a liposome.

RECOMBINANT RSV ANTIGENS

This disclosure provides recombinant respiratory syncytial virus (RSV) antigens and methods for making and using them, including immunogenic compositions (e.g., vaccines) for the treatment and/or prevention of RSV infection.

IMMUNOGENIC COMPOSITION

The present application relates to immunogenic compositions comprising a mixture of staphylococcal antigens which combines antigen having different functions, for instance, combinations including a staphylococcal extracellular component binding protein and a staphylococcal transporter protein or a staphylococcal extracellular component binding protein and a staphylococcal regulator of virulence or toxin or a staphylococcal transporter protein and a staphylococcal regulator of virulence or toxin. Vaccines, methods of treatment, uses of and processes to make a staphylococcal vaccine are also described.

COMPOSITION AND USE THEREOF FOR TREATING OR PREVENTING LATENT TUBERCULOSIS

The present invention is directed to a polypeptide which comprises (i) an Rv3616c protein sequence, (11) a variant of an Rv3616c protein sequence, or (111) an immunogenic fragment of an Rv3616c protein sequence for use in the treatment or prevention of latent TB In other aspects the invention is directed to associated polynucleotides, fusion proteins and methods for the treatment or prevention of latent tuberculosis ...

VACCINE AGAINST HPV

The use of HPV 16 and HPV 18 virus like particles (VLPs) together with a pharmaceutically acceptable excipient, m a vaccine for the prevention of human papillomavirus related disease or infection, wherein the vaccine is formulated for administration according to a two dose regimen consisting of a first dose and a second dose.

TREATMENT OF STAPHYLOCOCCI INFECTIONS USING RECOMBINANT FIBRINOGEN BINDING PROTEIN CLUMPING FACTOR A

The present invention is directed to improved microbial antigen vaccines, pharmaceutical compositions, immunogenic compositions and antibodies and their use in the treatment of microbial infections, particularly those of bacterial origin, including Staphylococcal origin. Ideally, the present invention is directed to a recombinant staphylococcal MSCRAMM or MSCRAMM-like proteins, or fragment thereof, with reduced binding to its host ligand, for use in therapy.

FUSION PROTEINS AND COMBINATION VACCINES COMPRISING HAEMOPHILUS INFLUENZAE PROTEIN E AND PILIN A

The present invention relates to compositions comprising Haemophilus influenzae Protein E and Pilin A. More particularly, the present application relates to fusion proteins and immunogenic compositions comprising Protein E and PilA, vaccines comprising such immunogenic compositions and therapeutic uses of the same.

IMMUNOGENIC COMPOSITION

NOVEL COMPOSITIONS AND METHODS

RECOMBINANT RSV ANTIGENS

E. coli taşıyıcı proteinlerine konjuge polisakkarit immünojenler.

ANTIGEN PURIFICATION METHOD

Methods, compositions, processes, and uses related to recombinant RSV soluble F protein polypeptides are provided.

OIL/SURFACTANT MIXTURES FOR SELF-EMULSIFICATION

Methods of manufacturing squalene and alpha-tocopherol-containing oil-in-water emulsions having small oil droplet particle sizes. Such emulsions being of use as vaccine adjuvants. 1. A composition comprising squalene , a tocopherol and a biocompatible metabolisable surfactant , wherein the squalene is 40% v/v or more of the composition , the tocopherol is 25% v/v or less of the composition , the surfactant is 60% v/v or less of the composition , which when mixed with an excess volume of substantially surfactant-free aqueous material , forms an adjuvant having an average oil particle diameter of 200 nm or less.24-. (canceled)5. A composition comprising squalene , a tocopherol and a biocompatible metabolisable surfactant , wherein the squalene is 50 to 70% v/v of the composition , the tocopherol is 10 to 20% v/v of the composition and the surfactant is 10 to 40% v/v of the composition.6. The composition according to claim 5 , wherein the squalene is 55 to 65% v/v of the composition claim 5 , the tocopherol is 10 to 20% v/v of the composition and the surfactant is 20 to 30% v/v of the composition.78-. (canceled)9. A method for preparing an oil-in-water emulsion adjuvant comprising squalene claim 1 , a tocopherol claim 1 , a biocompatible metabolisable surfactant and an aqueous component claim 1 , said method comprising mixing a composition according to with an excess volume of an aqueous component.10. The method of claim 9 , wherein the aqueous component comprises an antigen or antigenic component.11. The method of claim 10 , further comprising a step of drying the oil-in-water emulsion claim 10 , such as by lyophilisation.12. (canceled)13. A dried composition obtainable by the method of .14. An oil-in-water emulsion adjuvant composition comprising squalene claim 11 , a tocopherol claim 11 , a biocompatible metabolisable surfactant and an excess volume of an aqueous component claim 11 , wherein the squalene is 40% v/v or more of the total amount of squalene claim 11 , ...

Chemically defined medium for the industrial scale culture of a species of Bordetella

Chemically defined media for the industrial-scale culture of Bordetella species.

Immunogenic composition

The present application relates to an immunogenic composition comprising at least 2 conjugates of N. meningitidis capsular saccharide and protein carrier, wherein said conjugates comprise at least 2 different N. meningitidis capsular saccharides selected from the group consisting of MenA, MenC, MenY and MenW, wherein at least one capsular saccharide is conjugated to a protein carrier with a saccharide:protein ratio (w/w) between 1:2-1:5, and wherein at least one different capsular saccharide is conjugated to a protein carrier with a saccharide:protein ratio (w/w) between 5:1-1:1.99.

Purification of streptococcal capsular polysaccharide

A purification method for the capsular polysaccharide of type II GBS in which the capsular polysaccharide is filtered using a membrane with a cut-off of less than 30 kDa.

Immunogenic composition comprising elements of C. difficile CDTb and/or CDTa proteins

The present invention relates to immunogenic compositions comprising isolated Clostridium difficile CDTb and/or CDTa protein. In particular the isolated Clostridium difficile CDTb protein is suitably a truncated CDTb protein comprising the receptor binding domain or a mutated CDTb protein incapable of binding to CDTa, and the isolated Clostridium difficile CDTa protein is suitably a truncated CDTa protein which does not comprise the C-terminal domain. In particular the invention also relates to fusion proteins comprising a CDTa protein and a CDTb protein and also fusion proteins between an isolated Clostridium difficile toxin A protein and/or an isolated Clostridium difficile toxin B protein fused to a CDTb protein.

DELIVERY OF RNA TO TRIGGER MULTIPLE IMMUNE PATHWAYS

RNA encoding an immunogen is co-delivered to non-immune cells as the site of delivery and also to immune cells which infiltrate the site of delivery. The responses of these two cell types to the same delivered RNA lead to two different effects, which interact to produce a strong immune response against the immunogen. The non-immune cells translate the RNA and express the immunogen. Infiltrating immune cells respond to the RNA by expressing type I interferons and pro-inflammatory cytokines which produce a local adjuvant effect which acts on the immunogen-expressing non-immune cells to upregulate major histocompatibility complex expression, thereby increasing presentation of the translated protein to T cells. The effects on the immune and non-immune cells can be achieved by a single delivery of a single RNA e.g. by a single injection.

RNA vaccine against SARS-CoV-2 variants

The present invention is directed to a nucleic acid suitable for use in treatment or prophylaxis of an infection with a coronavirus, preferably with a Coronavirus SARS-CoV-2, or a disorder related to such an infection, preferably COVID-19. The present invention is also directed to compositions, polypeptides, and vaccines. The compositions and vaccines preferably comprise at least one of said nucleic acid sequences, preferably nucleic acid sequences in association a lipid nanoparticle (LNP). The invention is also directed to first and second medical uses of the nucleic acid, the composition, the polypeptide, the combination, the vaccine, and the kit, and to methods of treating or preventing a coronavirus infection, preferably a Coronavirus infection.

STAPHYLOCOCCUS AUREUS ANTIGEN

A negatively-charged S. aureus antigen contains .beta.-hexosamine as a major carbohydrate component. S. aureus strains that carry the antigen account for nearly all of the clinically significant strains of S. aureus that are not Type 5 ou Type 8 strains. The antigen can be used in combination with S. aureus Type 5 polysaccharide antigen and S. aureus Type 8 polysaccharide antigen to provide nearly 100% coverage of S. aureus infection. The antigen also is useful in kits and assays for diagnosing S. aureus infection.

IMMUNOGENIC COMPOSITION COMPRISING 1 OR MORE STREPTOCOCCUS PNEUMONIAE CAPSULAR SACCHARIDE CONJUGATES AND A PROTEIN COMPONENT COMPRISING PROTEIN E AND/OR PILA FROMHAEMOPHILUS INFLUENZAE

The present invention relates to immunogenic compositions comprising one or more Streptococcus pneumoniae capsular saccharide conjugates and a protein component comprising Protein E and/or Pil A from Haemophilus influenzae.

STAPHYLOCOCCUS ANTIGEN AND VACCINE

A negatively-charged Staphylococcus antigen contains amino acids and a N- acetylated hexosamine as a major carbohydrate component. The antigen is common to many coagulase-negative strains of Staphylococcus, including S. epidermidis, S. haemolyticus and S. hominis. Staphylococcus strains that carry the antigen include many clinically significant strains of Staphylococcus. The antigen and antibodies to the antigen are useful in kits and assays for diagnosing Staphylococcus infection. Vaccines of the antigen and of whole cells that carry the antigen are also disclosed.

PERIPLASMIC EXPRESSION OF DIPHTHERIA TOXINS

Compositions and methods related to periplasmic expression of a toxin including diphtheria toxin or CRM197 are provided herein.

A PROCESS FOR THE PURIFICATION OR PRODUCTION OF A MAGE PROTEIN

Uses of parasite macrophage migration inhibitory factors

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

Injectable vaccines against multiple meningococcal serogroups

An injectable immunogenic composition comprising capsular saccharides from at least two of serogroups A, C, W135 and Y of Neisseria meningitidis, wherein said capsular saccharides are conjugated to carrier protein(s) and/or are oligosaccharides, and wherein (i) the composition comprises <50 μg meningococcal saccharide per dose, and/or (ii) the composition further comprises an antigen from one or more of: (a) serogroup B N. meningitidis; (b) Haemophilus influenzae type B; and/or (c) Streptococcus pneumoniae. Saccharide antigens in the compositions are generally conjugated to a carrier.

Modified meningococcal fHbp polypeptides

Modified meningococcal fHbp polypeptides with increased stability.

PURIFICATION OF STREPTOCOCCAL CAPSULAR POLYSACCHARIDE

A purification method for the capsular polysaccharide of type II GBS in which the capsular polysaccharide is filtered using a membrane with a cut-off of less than 30 kDa.

Vaccine comprising Streptococcus pneumoniae capsular polysaccharide conjugates

The present invention relates to an immunogenic composition comprising S. pneumoniae capsular saccharide conjugates from serotypes 19A and 19F wherein 19A is conjugated to a first bacterial toxoid and 19F is conjugated to a second bacterial toxoid. Methods of making and uses thereof are also described.

Zika viral antigen constructs

Compounds useful as components of immunogenic compositions for the induction of an immunogenic response in a subject against viral infection, methods for their use in treatment, and processes for their manufacture are provided herein. The compounds comprise a nucleic acid construct comprising a sequence which encodes a Zika virus antigen. A particular embodiment is a nucleic acid-based vaccine construct encoding a polypeptide comprising a full-length Zika virus prME antigen. A particular embodiment is a self-replicating RNA molecule comprising a construct encoding a polypeptide comprising a full-length Zika virus prME antigen.

Methods for the induction of ebola virus-specific immune responses comprising administering a replication-defective chimpanzee adenovirus vector expressing the ebola virus glycoprotein

This invention provides vaccines for inducing an immune response and protection against filovirus infection for use as a preventative vaccine in humans. In particular, the invention provides chimpanzee adenoviral vectors expressing filovirus proteins from different strains of Ebola virus (EBOV) or Marburg virus (MARV).

Vaccines

The present invention provides vaccine compositions comprising an oil-in-water emulsion optionally with 3 De-O-acylated monophosphoryl lipid A and QS21. The vaccine compositions are potent induces of a range of immune responses.

FUSION PEPTIDES WITH ANTIGENS LINKED TO SHORT FRAGMENTS OF INVARIANT CHAIN(CD74)

The present application provides inter alia a fusion protein comprising a polypeptide wherein the polypeptide consists of a fragment of invariant chain which is operably linked to an antigenic sequence and wherein the fragment of invariant chain consists of a portion of residues 17-97 of SEQ ID NO: 1, wherein the portion comprises at least 5 contiguous residues from residues 77-92 of SEQ ID NO: 1.

Poxviral vaccines

The present application relates to novel administration regimens for poxviral vectors comprising nucleic acid constructs encoding antigenic proteins and invariant chains. In particular the use of said poxviral vectors for priming or for boosting an immune response is disclosed.

Hyperblebbing Shigella strains

Hyperblebbing Shigella strains are generated by disrupting one or more components of the Tol-Pal system. The blebs from these strains are useful immunogens for vaccination. The individual proteins found in these blebs can also be used as immunogens.

IMMUNOGENIC COMPOSITIONS

The present invention relates to carrier-formulated mRNA comprising at least one coding sequence encoding an influenza HA stem polypeptide, and to related aspects.

GLYCOCONJUGATE VACCINES FOR USE IN IMMUNE-COMPROMISED POPULATIONS

... ²²²Staphylococcal and Enterrococcal glycoconjugate vaccines are disclosed for use ²in preventing or treating bacterial infection in an immune-compromised ²individual. Such vaccines contain an immunocarrier and a conjugate of a ²polysaccharide or glycopeptide surface antigen from a clinically-significant ²bacterial strain. The vaccines can be used for active protection in immune-²compromised individuals who are to be subjected to conditions that place them ²at immediate risk of developing a bacterial infection, as would be case in the ²context of a catheterization or a surgical procedure.² ...

NOVEL METHOD AND COMPOSITIONS

The present invention relates to, inter alia, a method of raising an immune response against a pathogen which comprises administering (i) one or more first immunogenic polypeptides derived from said pathogen; (ii) one or more adenoviral vectors comprising one or more heterologous polynucleotides encoding one or more second immunogenic polypeptides derived from said pathogen; and (iii) an adjuvant; wherein the one or more first immunogenic polypeptides, the one or more adenoviral vectors and the adjuvant are administered concomitantly. The invention also relates to vaccines, pharmaceutical compositions, kits and uses employing said polypeptides, adenoviral vectors and adjuvants.

METHOD FOR DETERMINING A CONCENTRATION OF A POLYSORBATE SPECIES IN A MIXTURE

A method for determining a concentration of a polysorbate species, such as polysorbate 20, polysorbate 40, polysorbate 60, or polysorbate 80, in a mixture comprises obtaining a test sample of said mixture, adding an internal standard, preferably azide, to said test sample, obtaining, with a spectrometer, a mid-infrared Attenuated Total Reflectance (ATR) spectrum of the test sample, e.g. by using and ATR-FTIR apparatus, identifying, from the reflectance spectrum, a wavenumber corresponding to the C=0 peak (e. g., 1735 cm-1), identifying, from the reflectance spectrum, a wavenumber corresponding to the internal standard, calculating the area under the curve for said C=O wavenumber, normalized by the internal standard, and comparing said area to a calibration curve to determine the concentration of polysorbate in said test sample.

METHOD OF DETOXIFICATION OF PNEUMOLYSIN

The present invention relates to a method for purifying bacterial cytolysins such as pneumococcal pneumolysin. A single chromatography step produces excellent purification of the cytolysin by binding soluble aggregated cytolysin to a hydrophobic interaction chromatography material in the presence of detergent and high salt.

LIPIDATED OXOADENINE DERIVATIVES

IMMUNOGENIC COMPOSITION

Cationic oil-in-water emulsions

This invention generally relates to cationic oil-in-water emulsions that contain high concentrations of cationic lipids and have a defined oil:lipid ratio. The cationic lipid can interact with the negatively charged molecule thereby anchoring the molecule to the emulsion particles. The cationic emulsions described herein are useful for delivering negatively charged molecules, such as nucleic acid molecules to cells, and for formulating nucleic acid-based vaccines.

Simian adenoviral vectors encoding malaria antigen

The invention provides recombinant adenoviral vectors which are capable of eliciting immunity against the pre-erythrocytic stage of the life cycle of the malaria parasite. In particular, the invention provides a recombinant, replication deficient simian adenoviral vector which encodes an antigen comprising the thrombospondin-related adhesion protein (TRAP), and also immunogenic compositions (e.g. vaccines) comprising the vector and methods of using such compositions.

Immunodiffusion assay for influenza virus

A method for performing an immunodiffusion assay comprising at least the following steps of: (a) preparing one or more test samples comprising an influenza virus antigen, (b) treating the test samples with at least 5% (w/v) of detergent, (c) applying the treated test samples to a gel comprising an antibody specific to the influenza virus antigen, and (d) allowing the samples to diffuse into the gel.

DELIVERY OF RNA TO TRIGGER MULTIPLE IMMUNE PATHWAYS

RNA encoding an immunogen is co-delivered to non-immune cells at the site of delivery and also to immune cells which infiltrate the site of delivery. The responses of these two cell types to the same delivered RNA lead to two different effects, which interact to produce a strong immune response against the immunogen. The non-immune cells translate the RNA and express the immunogen. Infiltrating immune cells respond to the RNA by expressing type I interferons and pro-inflammatory cytokines which produce a local adjuvant effect which acts on the immunogen-expressing non-immune cells to upregulate major histocompatibility complex expression, thereby increasing presentation of the translated protein to T cells. The effects on the immune and non-immune cells can be achieved by a single delivery of a single RNA e.g. by a single injection.

IMMUNOGENIC COMPOSITION COMPRISING STAPHYLOCOCCUS AUREUS SACCHARIDES

The present application relates to immunogenic compositions comprising Type 5 and/or 8 capular polysaccharide or oligosaccharide from S. aureus having between 30-100% O- acetylation. Vaccines, methods of treatment using and processes to make an immunogenic composition comprising Type 5 and/or 8 capsular polysaccharides with 30-100% O- acetylation are also described.

METHOD OF LIPOPOLYSACCHARIDE EXTRACTION

The present invention provides a method of lipopolysaccharide (LPS) extraction from gram negative bacterial cells comprising the step: extracting LPS from the cell culture in a composition (LPS extraction composition) comprising water, an alcohol and a further organic solvent.

PNEUMOCOCCAL POLYSACCHARIDE CONJUGATE VACCINE

The present invention is in the field of pneumococcal capsular saccharide conjugate vaccines. Specifically, a multivalent Streptococcus pneumoniae immunogenic composition is provided with various conjugated capsular saccharides from different S. pneumoniae serotypes conjugated to 2 or more different carrier proteins, where the composition comprises serotype 19F capsular saccharides conjugated to diphtheria toxoid (DT) or CRM197, optionally wherein 19F is the only saccharide in the composition conjugated to diphtheria toxoid (DT) or CRM197.

PROCESS FOR THE PURIFICATION OF SAPONINS

The present invention provides methods for purifying at least one saponin in a solution comprising the steps of: (a) providing at least one saponin in a first solvent comprising a solubilizing component; (b) replacing at least a portion of the solubilizing component with an exchange solvent, thereby producing a replaced solvent; and (c) removing the replaced solvent, to produce a dried saponin product comprising at least one saponin.

NOVEL METHOD AND COMPOSITIONS

The present invention relates to, inter alia, a method of raising an immune response against a pathogen which comprises administering (i) one or more first immunogenic polypeptides derived from said pathogen; (ii) one or more adenoviral vectors comprising one or more heterologous polynucleotides encoding one or more second immunogenic polypeptides derived from said pathogen; and (iii) an adjuvant; wherein the one or more first immunogenic polypeptides, the one or more adenoviral vectors and the adjuvant are administered concomitantly. The invention also relates to vaccines, pharmaceutical compositions, kits and uses employing said polypeptides, adenoviral vectors and adjuvants.

MALARIA PRIME/BOOST VACCINES

IMPROVED POXVIRAL VACCINES

Immunogenic proteins and compositions

The invention provides proteins and compositions for the treatment and prevention of Streptococcus agalactiae (Group B streptococcus; GBS).

Expression system

Compositions and methods related to periplasmic expression of a toxin including diphtheria toxin or CRM197 are provided herein.

Vaccine composition comprising virus-like particles of human papillomavirus

The present invention relates to a vaccine composition comprising VLPs containing L1 proteins or functional L1 protein derivatives from HPV 16, HPV 18, HPV 31 and HPV 45 genotypes.

SAPONIN PURIFICATION

Saponin extracts containing at least 88% QS-21 main peak and >3% to 10% 2018 component by UV absorbance at 214 nm, methods for making said extracts, their use as vaccine adjuvants and related aspects.

VARICELLA ZOSTER VIRUS VACCINE

Use of an immunogenic composition comprising VZV gE, or immunogenic fragment thereof, and a TH-1 adjuvant in the preparation of a medicament for the prevention or amelioration of shingles and/or post herpetic neuralgia. Compositions comprising a truncated VZV gE antigen and an adjuvant containing QS21, cholesterol and 3D MPL are also claimed.

ACTIVATION OF HCV-SPECIFIC T CELLS

Methods for activating HCV-specific T cells are described. The methods utilize one or more administrations of HCV protein compositions, followed by one or more administrations of a viral vector comprising a nucleic acid encoding a least one HCV epitope that is present in the first composition. The protein compositions can further comprise an immunostimulatory nucleic acid and or other adjuvants and immune stimulatory compounds.

Animal-free cell culture method

The present invention relates to a process for culturing animal cells, e.g., human, diploid anchorage-dependent cells, in the absence of exogenous components of primary animal origin. In particular, the invention provides cell culture media substantially free of exogenous components of primary and secondary animal origin which comprises at least one, more preferably several, exogenous animal-free growth factors. The present invention also relates to a process for cultivating animal cells using a protease of non-animal origin for passaging cells.

Immunogenic composition comprising antigenic s. aureus proteins

The present application relates to an immunogenic composition comprising a fragment of a staphylococcal Isd protein such as IsdA, IsdB, IsdC or IsdH which comprises a NEAT domain. Fusion proteins comprising a NEAT domain of a first staphylococcal Isd protein and a NEAT domain from a second Isd protein are also disclosed as well as fusion proteins comprising a NEAT domain of a staphylococcal Isd protein involved in an iron/heme uptake system and a ligand binding domain of a staphylococcal extracellular component binding protein, for example ClfA, ClfB, SdrC, SdrD or SdrE.

Polyanionic polymer adjuvants for haemophilus influenzae b saccharide vaccines

The present invention relates to immunogenic compositions comprising capsular polysaccharide or oligosaccharide of H. influenzae B (PRP) and methods of making such compositions.

Novel compounds

The invention provides BASB082, BASB083, BASB091, BASB092 and BASB101 polypeptides and polynucleotides encoding BASB082, BASB083, BASB091, BASB092 and BASB101 polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are diagnostic, prophylactic and therapeutic uses.

Treatment of streptococcal infections

Immunogenic compositions and methods of treating a Streptococcus pneumoniae infection are described herein.

Process for manufacturing vaccines

The present application discloses an improved method for conducting saccharide—protein conjugation reactions using carbodiimide condensation chemistry. Depending on the nature of the saccharide or protein carrier involved, the quality of the conjugate may be improved by adding one of the reaction components slowly to the reaction mixture. Immunogenic compositions are further provided comprising the saccharide-protein conjugates made by the methods disclosed.

Immunogenic composition

Compositions for the treatment or prevention of Neisserial infection and methods for their use and manufacture are provided herein.

Oral vaccine compromising an antigen and a toll-like receptor agonist

The present invention provides an immunogenic composition comprising one or more antigens and a Toll-like receptor (TLR) agonist in an orally (e.g. sublingually) administered composition.

Immunogenic composition

The present application discloses an immunogenic composition comprising a Hib saccharide conjugate, at least one additional bacterial, for example N. meningitidis, saccharide conjugate(s), and a further antigen selected from the group consisting of whole cell pertussis and hepatitis B surface antigen, wherein the saccharide dose of the Hib saccharide conjugate is less than 5 μg.

Cytomegalovirus gb antigen

The invention relates to a cytomegalovirus (CMV) gB polypeptide comprising at least a portion of a gB protein extracellular domain comprising a fusion loop 1 (FL1) domain and a fusion loop 2 (FL2) domain, wherein at least one of the FL1 and FL2 domains comprises at least one amino acid deletion or substitution.

Vaccine composition

The present invention relates to DTP-based combination vaccine formulations, and concomitantly administered combination vaccine kits. Methods of administration of these vaccines and kits are also provided.

PROCESS FOR PRODUCING AN IMMUNOGENIC COMPOSITION CONTAINING TETANUS TOXOID

The present invention relates to the field of vaccines for protecting against tetanus, and in particular processes for the production of vaccines comprising tetanus toxoid adsorbed onto aluminium salts. Processes are provided whereby tetanus toxoid is absorbed onto aluminium salt adjuvant having defined characteristics for optimal results. 1. A process for producing an immunogenic composition comprising tetanus toxoid comprising the step of adsorbing the tetanus toxoid onto an aluminium salt particle wherein the aluminium salt particle has a protein adsorption capacity of between 2.5 and 3.7 , 2.6 and 3.6 , 2.7 and 3.5 , or 2.8 and 3.4.2. The process of wherein the aluminium salt particle has a protein adsorption capacity of between 2.5 and 3.5 claim 1 , 2.6 and 3.4 claim 1 , 2.7 and 3.3 or 2.9 and 3.2.3. The process according to wherein the aluminium salt has a crystal size of between 2.8 and 5.7 nm as measured by X-ray diffration.4. The process according to wherein the aluminium salt has a crystal size of between 3.3 and 5.7 nm as measured by X-ray diffraction.5. The process according to wherein the aluminium salt particle has a protein adsorption capacity of between 2.5 and 3.6 and a crystal size of between 2.9 and 5.6 nm.6. A process for producing an immunogenic composition comprising tetanus toxoid comprising the step of adsorbing the tetanus toxoid onto an aluminium salt particle wherein the aluminium salt particle has a crystal size of between 2.8 and 5.7 nm as measured by X-ray diffraction.7. The process according to for producing an immunogenic composition comprising tetanus toxoid further comprising the step of adsorbing the diphtheria toxoid onto a second aluminium salt particle wherein the second aluminium salt particle to which the diphtheria toxoid is adsorbed has a protein adsorption capacity of between 2.5 and 3.5 claim 1 , 2.6 and 3.4 claim 1 , 2.7 and 3.3 or 2.9 and 3.2.8. The process according to wherein the second aluminium salt particle to which ...

FUSION PROTEINS AND COMBINATION VACCINES COMPRISING HAEMOPHILUS INFLUENZAE PROTEIN E AND PILIN A

The present invention relates to compositions comprising Protein E and Pilin A. More particularly, the present application relates to fusion proteins and immunogenic compositions comprising Protein E and PilA, vaccines comprising such immunogenic compositions and therapeutic uses of the same. 19-. (canceled)10. A fusion protein selected from the group consisting of SEQ ID NO. 136 , SEQ ID NO. 138 , SEQ ID NO. 140 , SEQ ID NO. 142 , SEQ ID NO. 144 , SEQ ID NO. 146 , SEQ ID NO. 148 , SEQ ID NO. 150 , SEQ ID NO. 182 , SEQ ID NO. 184 , SEQ ID NO. 186 , SEQ ID NO. 188 , SEQ ID NO. 190 , SEQ ID NO. 192 , SEQ ID NO. 194 , SEQ ID NO. 196 , SEQ ID NO. 198 , SEQ ID NO. 200 , SEQ ID NO. 202 and SEQ ID NO. 204.11. (canceled)12. A fusion protein of wherein the signal peptide has been removed.13. The fusion protein of SEQ ID NO. 148 wherein the signal peptide has been removed claim 10 , SEQ ID NO. 177 (QIQKAEQN DVKLAPPTDV RSGYIRLVKN VNYYIDSESI WVDNQEPQIV HFDAVVNLDK GLYVYPEPKR YARSVRQYKI LNCANYHLTQ VRTDFYDEFW GQGLRAAPKK QKKHTLSLTP DTTLYNAAQI ICANYGEAFS VDKKGGTKKA AVSELLQASA PYKADVELCV YSTNETTNCT GGKNGIAADI TTAKGYVKSV TTSNGAITVK GDGTLANMEY ILQATGNAAT GVTWTTTCKG TDASLFPANF CGSVTQ).14. The fusion protein of SEQ ID NO. 194 wherein the signal peptide has been removed claim 10 , SEQ ID NO. 219 (IQKAEQND VKLAPPTDVR SGYIRLVKNV NYYIDSESIW VDNQEPQIVH FDAVVNLDKG LYVYPEPKRY ARSVRQYKIL NCANYHLTQV RTDFYDEFWG QGLRAAPKKQ KKHTLSLTPD TTLYNAAQII CANYGEAFSV DKKGGTKKAA VSELLQASAP YKADVELCVY STNETTNCTG GKNGIAADIT TAKGYVKSVT TSNGAITVKG DGTLANMEYI LQATGNAATG VTWTTTCKGT DASLFPANFC GSVTQ).1522-. (canceled)23. An immunogenic composition comprising the fusion protein of SEQ ID NO. 177 (QIQKAEQN DVKLAPPTDV RSGYIRLVKN VNYYIDSESI WVDNQEPQIV HFDAVVNLDK GLYVYPEPKR YARSVRQYKI LNCANYHLTQ VRTDFYDEFW GQGLRAAPKK QKKHTLSLTP DTTLYNAAQI ICANYGEAFS VDKKGGTKKA AVSELLQASA PYKADVELCV YSTNETTNCT GGKNGIAADI TTAKGYVKSV TTSNGAITVK GDGTLANMEY ILQATGNAAT GVTWTTTCKG TDASLFPANF CGSVTQ).24. An immunogenic composition comprising the ...

Vaccine against streptococcus pneumoniae

The present invention relates to a combination of 2 or more S pneumoniae proteins, their manufacture and use in medicine as a vaccine. Such combinations are particularly useful for the protection of infants and elderly against streptococcal infection.

COMPOSITIONS AND METHODS FOR PROTEIN GLYCOSYLATION

Described herein are oligosaccharyl transferases for use in N-glycosylating proteins of interest in vitro and in host cells. Methods for using such oligosaccharyl transferases, nucleic acids encoding such oligosaccharyl transferases, and host cells comprising such oligosaccharyl transferases are also provided herein. Glycoconjugates generated by using such oligosaccharyl transferases are also provided herein. 116-. (canceled)17. A recombinant N-oligosaccharyl transferase , wherein the recombinant N-oligosaccharyl transferase (N-OST) can detectably link an oligosaccharide or polysaccharide lacking an N-acetyl sugar at the reducing end to a carrier protein at an N-glycosylation consensus sequence wherein one or more amino acids selected from the group consisting of Y77 , S80 , 5196 , N311 , Y462 , K482 , D483 and G477 of Pg1Bare modified .18Campylobacter jejuniCampylobacter lari. The recombinant N-oligosaccharyl transferase of claim 17 , wherein the recombinant N-oligosaccharyl transferase is Pg1B of (Pg1B) or Pg1B of (Pg1B ).19. The recombinant N-oligosaccharyl transferase of claim 17 , wherein the recombinant N-oligosaccharyl transferase comprises a modification in one or more amino acids whose side chains are located within a 2.5-4.0 Å distance from one of the three terminal monosaccharide units at the reducing end of the oligosaccharide or polysaccharide component of a bound N-glycosylated carrier protein in a structural model of a complex of the recombinant N-oligosaccharyl transferase and the N-glycosylated carrier protein.20. The recombinant N-oligosaccharyl transferase of claim 17 , wherein recombinant N-oligosaccharyl transferase comprises modification in two or more amino acids.21. The recombinant N-oligosaccharyl transferase of claim 17 , wherein at least one of the one or more amino acids is located in a periplasmatic loop of a transmembrane domain of the recombinant N-oligosaccharyl transferase.22. The recombinant N-oligosaccharyl transferase of claim 18 ...

MULTI-FUNCTIONALIZED noMV CONJUGATES

The present invention is in the field of conjugating native, non-detergent extracted, outer membrane vesicles (nOMV) to multiple antigens to form multi functionalized nOMV-antigen conjugated derivatives, which are particularly useful for immunogenic compositions and immunisation; processes for the preparation and use of such conjugates are also provided. 1. An immunogenic conjugate comprising a native outer membrane vesicle (nOMV) , having at least a surface saccharide moiety connected to an antigen , and at least a surface protein residue connected to a different antigen through a bivalent linker.2. The derivative according to claim 1 , wherein said bivalent Linker has the general formula (I):{'br': None, 'X-L-X′\u2003\u2003(I)'}wherein:X and X′ are different to each other or the same, and are a functional group able to selectively react with the nOMV protein residue on one hand and with the antigen on the other hand;{'sub': 1', '15, '-L- is a bivalent linear or branched C-Calkyl or alkenyl group optionally substituted, and optionally interrupted by one or more heteroatom selected from: oxygen (—O—), sulfur (—S—), nitrogen (—NH— or optionally substituted —N— group) and the like.'}3. The conjugate according to claim 2 , wherein said bivalent Linker is a homobifunctional Linker having X=X′.4. The conjugate according to claim 2 , wherein said bivalent Linker is selected from at least one of: disuccinimidyl glutarate (DSG) claim 2 , disuccinimidyl suberate (DSS) claim 2 , succinimidyl 3-(2-pyridyldithio)propionate (SPDP) claim 2 , Succinimidyl 6-(3-[2-pyridyldithio]-propionamido)hexanoate (LC-SPDP) claim 2 , sulfosuccinimidyl 6-(3′-(2-pyridyldithio)propionamido)hexanoate (sulfo-LC-SPDP) claim 2 , 4-succinimidyloxycarbonyl-α-methyl-α-(2-pyridyldithio)toluene (SMPT) claim 2 , sulfosuccinimidyl-6-[α-methyl-α-(2-pyridyldithio)tolueamideo]hexanoate (sulfo-LC-SMPT) claim 2 , succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC) claim 2 , sulfosuccinimidyl 4-(N- ...

USPA2 PROTEIN CONSTRUCTS AND USES THEREOF

The present invention relates to compositions comprising () Ubiquitous surface protein A2 (UspA2). More particularly, the present application relates to UspA2 protein constructs and immunogenic compositions comprising the constructs, vaccines comprising such immunogenic compositions and therapeutic uses of the same. The invention further relates to compositions comprising UspA2 in combination with at least one antigen from , immunogenic compositions comprising the antigens, vaccines comprising such immunogenic compositions and therapeutic uses of the same. 114.-. (canceled)15. A protein selected from the group consisting of SEQ ID NO: 53 , SEQ ID NO: 55 , SEQ ID NO: 57 , SEQ ID NO: 59 , SEQ ID NO: 61 , SEQ ID NO: 63 , SEQ ID NO: 65 , SEQ ID NO: 67 , SEQ ID NO: 69 , SEQ ID NO: 71 , SEQ ID NO: 73 and SEQ ID NO: 88.1621.-. (canceled)22. An immunogenic composition comprising a protein selected from the group consisting of SEQ ID NO: 53 , SEQ ID NO: 55 , SEQ ID NO: 57 , SEQ ID NO: 59 , SEQ ID NO: 61 , SEQ ID NO: 63 , SEQ ID NO: 65 , SEQ ID NO: 67 , SEQ ID NO: 69 , SEQ ID NO: 71 , SEQ ID NO: 73 and SEQ ID NO: 88.23Haemophilus influenzae.. An immunogenic composition of an of further comprising at least one antigen from24. The immunogenic composition of wherein the at least one antigen is Protein D.25. The immunogenic composition further comprising Protein E.26. The immunogenic composition of further comprising PilA.27. The immunogenic composition of wherein PE and PilA are present as a fusion protein.28. A vaccine comprising the immunogenic composition of .2932.-. (canceled)33. A method for the treatment or prevention of otitis media in a subject in need thereof comprising administering to said subject a therapeutically effective amount of an immunogenic composition according to .34. A method for the treatment or prevention of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in a subject in need thereof comprising administering to said subject a ...

MODIFIED MENINGOCOCCAL FHBP POLYPEPTIDES

Modified meningococcal fHbp polypeptides with increased stability. 1. A mutant v2 fHbp polypeptide comprising an amino acid sequence selected from:(a) a sequence having at least 80% sequence identity to SEQ ID NO: 5 and containing an amino acid residue corresponding to residue S32 of SEQ ID NO:5 that has been substituted with any other amino acid except alanine,(b) a sequence having at least 80% sequence identity to SEQ ID NO: 5 and containing an amino acid residue corresponding to residue S32 of SEQ ID NO:5 that has been substituted with any other amino acid, and further comprising a substitution at a position corresponding to V33, L39, L41, F69, V100, I113, F122, L123, V124, S125, G126, L127, G128, S151, H239, or E240 of SEQ ID NO:5,(c) a sequence comprising a fragment of SEQ ID NO: 5 which is at least 7 amino acids long and contains an amino acid residue corresponding to residue S32 of SEQ ID NO: 5 that has been substituted with any other amino acid except alanine, and(d) a sequence comprising a fragment of SEQ ID NO:5 which is at least 7 amino acids long and contains an amino acid residue corresponding to residue S32 of SEQ ID NO:5 that has been substituted with any other amino acid, and further comprising a substitution at a position corresponding to V33, L39, L41, F69, V100, I113, F122, L123, V124, S125, G126, L127, G128, S151, H239, or E240 of SEQ ID NO:5.2. The polypeptide of claim 1 , wherein: (A) the amino acid sequence is selected from:(a) a sequence that differs from SEQ ID NO: 5 by substitution at the position corresponding to S32 and at least one position corresponding to V33, L39, L41, F69, V100, I113, F122, L123, V124, S125, G126, L127, G128, S151, H239, or E240; and(b) a sequence that differs from SEQ ID NO:5 by substitutions of S32V and at least one of V33C; L39C; L41C; F69C; V100T; I113S; F122C; L123R; V124I; S125G or S125T; G126D; L127I; G128A; S151C; H239R; or E240H.3. The polypeptide of claim 1 , comprising amino acid substitutions at multiple ...

IMMUNOGENIC BACTERIAL VESICLES WITH OUTER MEMBRANE PROTEINS

Knockout of the meningococcal mltA homolog gives bacteria that spontaneously release vesicles that are rich in immunogenic outer membrane proteins and that can elicit cross-protective antibody responses with higher bactericidal titres than OMVs prepared by normal production processes. Thus the invention provides a bacterium having a knockout mutation of its mltA gene. The invention also provides a bacterium, wherein the bacterium: (i) has a cell wall that includes peptidoglycan; and (ii) does not express a protein having the lytic transglycosylase activity MltA protein. The invention also provides compositions comprising vesicles that, during culture of bacteria of the invention, are released into the culture medium. 125-. (canceled)26Escherichia bacterium. A process for preparing bacterial vesicles , comprising the steps of: (i) culturing an in a culture medium such that the bacterium releases vesicles into said medium; and (ii) collecting the vesicles from said medium , wherein: (a) the bacterium has a cell wall that includes peptidoglycan; and (b) the bacterium does not express a protein having the lytic transglycosylase activity of MltA protein.27. The process of claim 26 , wherein the bacterium also has a knockout mutation of at least one further gene.28E. coli.. The process of claim 26 , wherein the bacterium is29E. coli.. The process of claim 28 , wherein the bacterium is a pathogenic30E. coli. The process of claim 29 , wherein the pathogenic is an extraintestinal pathogenic bacterium claim 29 , a uropathogenic bacterium claim 29 , or a meningitis/sepsis-associated bacterium.31E. coli.. The process of claim 27 , wherein the bacterium is32E. coli.. The process of claim 31 , wherein the bacterium is a pathogenic33E. coli. The process of claim 32 , wherein the pathogenic is an extraintestinal pathogenic bacterium claim 32 , a uropathogenic bacterium claim 32 , or a meningitis/sepsis-associated bacterium.34Escherichia coli. The process of claim 26 , wherein the ...

MICROFLUIDIC DEVICES

The present invention relates broadly to microfluidic devices, particularly microfluidic devices optimised for the industrial production of nanoparticles such as liposomes. The device () comprises a substrate which extends between a distal end () comprising an outlet region () and a proximal end () comprising an inlet region (). The inlet region comprises two substantially parallel outer channels () for transport of a first fluid, said outer channels () defined in part by a first outer wall () and a second outer wall () respectively, and a linear inner channel () for transport of a second fluid. The linear channel is disposed between the two substantially parallel outer channels. The outer channels () and inner channel () extend from the proximal end () to a mixing chamber () which extends from the inlet region () to the outlet region (). The mixing chamber () is in flow communication with the inner and outer channels () to receive the first and second fluids from the inner and outer channels () and the mixing chamber () has a uniform width (W) along its length substantially equal to the width (W) between the outer walls () of the two substantially parallel outer channels (). 117-. (canceled)18. A microfluidic device comprising a mixing chamber having a distal end comprising an outlet region and a proximal end comprising an inlet region , the inlet region comprising two substantially parallel outer channels configured for transport of a first fluid and an inner channel configured for transport of a second fluid , wherein the inner channel is disposed between the two substantially parallel outer channels , and wherein the mixing chamber is configured to receive the first and second fluids from the inner and outer channels , and wherein the mixing chamber has rectangular cross-section with a long side 1600 μm±100 μm , a depth of 0.5 mm±40 μm , the width of the inner channel is 220 um to 500 um , the width of the two substantially parallel outer channels is about 150 μ ...

VACCINE

The present provide vaccine and adjuvant formulation comprising an immunostimulant and a metal salt. The immunostimulant is adsorbed on to a particle of metal salt and the resulting particle is essentially devoid of antigen. 1. A vaccine composition comprising two major populations of complexes , a first complex comprising (a) an immunostimulant which is 3-de-O-acylated monophosphoryl lipid A adsorbed onto an aluminum hydroxide or aluminum phosphate particle , characterized in that said aluminum salt particle is substantially free of antigen; and a second complex comprising (b) human papilloma virus L1 particles or capsomers adsorbed onto an aluminum hydroxide or aluminum phosphate particle , characterized in that the aluminum salt particle is substantially free of immunostimulant; and wherein the aluminum salt present in the first and second complexes are identical.2. The vaccine composition of wherein the antigen is derived from HPV6 claim 1 , HPV11 claim 1 , HPV16 or HPV18.3. The vaccine composition of wherein the antigen is derived from HPV16 or HPV18.4. The vaccine composition of wherein the aluminum salt is aluminum hydroxide.5. The vaccine composition of wherein the aluminum salt is aluminum hydroxide.6. The vaccine composition of wherein the aluminum salt is aluminum hydroxide.7. The vaccine composition of wherein the aluminum salt is aluminum phosphate.8. The vaccine composition of wherein the aluminum salt is aluminum phosphate.9. The vaccine composition of wherein the aluminum salt is aluminum phosphate. This application is a continuation of U.S. patent application Ser. No. 11/945,493 filed Feb. 28, 2008, now allowed, which is a continuation of U.S. patent application Ser. No. 09/807,657 filed Apr. 16, 2001 and issued as U.S. Pat. No. 7,357,936, filed pursuant to 35 USC 371 as a United States National Phase Application of International Patent Application PCT/EP99/07764 filed Oct. 8, 1999, which claims priority from 9822703.6, 9822709.3 and 9822712.7 all ...

ADJUVANT COMPOSITIONS COMPRISING A NON-IONIC ISOTONICITY AGENT

The present invention relates to an aqueous adjuvant composition comprising a TLR-4 agonist and a saponin in a liposomal formulation and a non-ionic isotonicity agent having low salt concentrations. 124.-. (canceled)25. An aqueous adjuvant composition comprising: (a) a TLR-4 agonist and a saponin in a liposomal formulation; and (b) a non-ionic isotonicity agent , wherein the concentration of sodium chloride or the ionic strength in the adjuvant composition is less than 100 mM.261. An aqueous adjuvant composition as claimed in claim wherein the concentration of sodium chloride or ionic strength is less than 80 mM.272. An aqueous adjuvant composition as claimed in claim wherein the concentration of sodium chloride or ionic strength is less than 30 mM.283. An aqueous adjuvant composition as claimed in claim wherein the concentration of sodium chloride or ionic strength is less than 10 mM.294. An aqueous adjuvant composition as claimed in claim wherein the concentration of sodium chloride or ionic strength is less than 5 mM.305. An aqueous adjuvant composition as claimed in claim which contains essentially no sodium chloride.311. An aqueous adjuvant composition according to claim wherein the non-ionic isotonicity agent is a polyol.327. An aqueous adjuvant composition according to claim wherein the polyol is sorbitol.338. The aqueous adjuvant composition of claim wherein the concentration of sorbitol is between about 3% and about 15% (w/v).349. An aqueous adjuvant composition of claim wherein the concentration of sorbitol is between about 4% and about 10% (w/v).351. The aqueous adjuvant composition of claim wherein said TLR-4 agonist is 3D-MPL.361. An aqueous adjuvant composition according to claim wherein said saponin is QuilA or a derivative thereof.3712. An aqueous adjuvant composition according to claim wherein the derivative of QuilA is QS21.381. An aqueous adjuvant composition according to claim comprising about 5 mM sodium chloride and between 5% and 6% w/v ...

IMMUNOGENIC COMPOSITION COMPRISING STAPHYLOCOCCAL ANTIGENS

The invention provides an immunogenic composition comprising staphylococcal antigens, containing protein antigens and conjugates of capsular polysaccharides, n particular Hla, ClfA, SpA and conjugates of capsular polysaccharides. Adjuvanted formulations are also provided. The invention may find use in the prevention and treatment of staphylococcal infections, in particular infection and disease. 1. An immunogenic composition comprisinga. a ClfA antigen;b. a Hla antigen;c. a SpA antigen; andd. a staphylococcal capsular polysaccharide.2. An immunogenic composition according to claim 1 , wherein the capsular polysaccharide is conjugated to a carrier protein.3S. aureus. An immunogenic composition according to claim 1 , wherein the capsular polysaccharide is a serotype 5 and/or type 8 capsular polysaccharide.4. An immunogenic composition according to claim 1 , wherein the capsular polysaccharide is conjugated to one of the antigens (a)-(c) of .5S. aureus. An immunogenic composition according to claim 1 , wherein the composition comprises a serotype 5 capsular polysaccharide and a type 8 capsular polysaccharide.6S. aureus. An immunogenic composition according to claim 1 , wherein the composition comprises a serotype 5 capsular polysaccharide conjugated to a Hla antigen and/or a type 8 capsular polysaccharide conjugated to a ClfA antigen.7. An immunogenic composition according to claim 1 , whereina. the ClfA antigen is a ClfA protein comprising the amino acid sequence of SEQ ID NO. 2 or an amino acid sequence at least 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO. 2, or immunogenic fragment thereof;b. the Hla antigen is a Hla protein having the amino acid sequence of SEQ ID NO. 3 or an amino acid sequence at least 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO. 3 or immunogenic fragment thereof; and/orc. the SpA antigen is a SpA protein having an amino acid sequence of SEQ ID NO. 13 or SEQ ID NO: 26_or an amino acid sequence at ...

PHOSPHOLIPIDATION OF IMIDAZOQUINOLINES AND OXOADENINES

The present invention relates to a process for phospholipidation of imidazoquinolines and oxoadenines. More particularly, the present invention relates to a high-yielding and scalable procedure for the phospholipidation of imidazoquinolines and oxoadenines which obviates the need to isolate unstable phosphoramidite intermediates. This process may be used for the phospholipidation of toll-like receptor 7 (TLR7)-active and toll-like receptor (TLR8)-active imidazoquinolines and oxoadenines. 211.-. (canceled)12. The process of wherein 1H-tetrazole is added to a compound of formula (III) or formula (IV).13. The process of wherein 1H-tetrazole is added in several portions over 20 to 40 minutes.14. The process of wherein imidazolium triflate is added with a compound of formula (VII) or (VIII).15. The process of wherein the coupling agent used with a compound of formula (III) or formula (IV) and a compound of formula (V) is at 2.1 equivalents claim 1 , the compound of formula (III) or formula (IV) is at 2.0 equivalents claim 1 , the compound of formula (V) is at 2.1 equivalents claim 1 , the compound of formula (VII) or formula (VIII) is at 1.0 equivalent and the oxidizing agent for the compound of formula (IX) is at 1.5 equivalent.16. The process of wherein imidazolium triflate is added with the compound of formula (VII) or the compound of formula (VIII) to the same reaction mixture produced by the reaction of compound of formula (V) with the compound of formula (III) or the compound of formula (IV).17. The process of wherein the reaction mixture containing the compound of formula (VI) is cooled to 0° C. before the addition of a compound of formula (VII) or formula (VIII).18. The process of wherein the hydroxyl protecting group is cyanoethyl and deprotection is with triethylamine (TEA).20. The process of wherein 1H-tetrazole is added to a compound of formula (III) or formula (IV).21. The process of wherein 1H-tetrazole is added in several portions over 20 to 40 minutes.22. ...

NEISSERIA MENINGITIDIS ANTIGENS AND COMPOSITIONS

The invention provides proteins from , including the amino acid sequences and the corresponding nucleotide sequences. The proteins are predicted to be useful antigens for vaccines and/or diagnostics. 1. (canceled)2. A protein comprising (i) a fragment of at least seven consecutive amino acids from an amino acid sequence selected from the group consisting of SEQ ID NO: 2916; SEQ ID NO: 2918 , and SEQ ID NO: 2920 , or (ii) an amino acid sequence having at least 80% identity to one of SEQ ID NO: 2916; SEQ ID NO: 2918 , and SEQ ID NO: 2920.3. The protein of comprising the fragment claim 2 , wherein the fragment comprises at least ten consecutive amino acids from an amino acid sequence selected from the group consisting of SEQ ID NO: 2916; SEQ ID NO: 2918 claim 2 , and SEQ ID NO: 2920.4. The protein of claim 3 , wherein the fragment comprises at least fourteen consecutive amino acids from an amino acid sequence selected from the group consisting of SEQ ID NO: 2916; SEQ ID NO: 2918 claim 3 , and SEQ ID NO: 2920.5. The protein of claim 3 , wherein the fragment comprises at least twenty consecutive amino acids from an amino acid sequence selected from the group consisting of SEQ ID NO: 2916; SEQ ID NO: 2918 claim 3 , and SEQ ID NO: 2920.6. The protein of comprising the amino acid sequence having at least 80% identity to one of SEQ ID NO: 2916; SEQ ID NO: 2918 claim 2 , and SEQ ID NO: 2920.7. The protein of claim 6 , wherein the amino acid sequence has at least 85% identity to one of SEQ ID NO: 2916; SEQ ID NO: 2918 claim 6 , and SEQ ID NO: 2920.8. A composition comprising the protein of and a pharmaceutically acceptable excipient.9. The composition of claim 8 , further comprising an adjuvant.10. The composition of claim 9 , wherein the adjuvant is an aluminum salt adjuvant.11. The composition of claim 10 , wherein the aluminum salt adjuvant comprises aluminum hydroxide.12. The composition of claim 9 , wherein the protein comprises the fragment and the fragment comprises at ...

OUTER MEMBRANE VESICLE (OMV) VACCINE COMPRISING N. MENINGITIDIS SEROGROUP B OUTER MEMBRANE PROTEINS

A composition comprising (a) serogroup B outer membrane vesicles (OMVs), and (b) an immunogenic component selected from other proteins, or immunogenic fragments thereof. Component (b) preferably includes a protein from a different NmB strain from that from which the OMV of component (a) is derived. The OMVs are preferably obtained by deoxycholate extraction. Optionally, the composition may also comprise a protective antigen against other pathogens. 1. (canceled)2. A composition comprising(a) an immunologically effective amount of at least one isolated protein comprising an amino acid sequence having at least 99% identity to the mature form of SEQ ID NO: 2536 of WO99/57280 or an immunogenic fragment comprising twenty or more consecutive amino acids of the mature form of the amino acid sequence of SEQ ID NO: 2536 of WO99/57280; and{'i': 'Neisseria meningitidis', '(b) a serogroup B outer membrane preparation comprising an immunologically effective amount of PorA.'}3. The composition of claim 2 , further comprising a pharmaceutically acceptable carrier claim 2 , adjuvant claim 2 , diluent or buffer.4. The composition of claim 3 , wherein said composition additionally comprises an adjuvant.5. The composition claim 2 , wherein the at least one isolated protein is a recombinant protein.6Neisseria. The composition of claim 2 , wherein the at least one isolated protein is isolated from native species.7. (canceled)8. The composition of claim 2 , wherein the at least one isolated protein is a fusion protein.9. The composition of claim 2 , wherein the at least one isolated protein is conjugated to a carrier such as a bacterial toxoid.10. The composition of claim 4 , wherein the adjuvant is aluminum hydroxide or aluminum phosphate.11. A composition comprising(a) at least one isolated protein comprising an amino acid sequence having at least 99% identity to the mature form of SEQ ID NO: 2536 of WO99/57280 or an immunogenic fragment comprising twenty or more consecutive amino ...

MULTIPLE VARIANTS OF MENINGOCOCCAL PROTEIN NMB1870

Meningococcal protein NMB 1870 has been described in the prior art. The inventors have found that NMB 1870 is an effective antigen for eliciting anti-meningococcal antibody responses, and that it is expressed across all meningococcal serogroups. Forty-two different NMB 1870 sequences have been identified, and these group into three variants. Serum raised against a given variant is bactericidal within the same variant group, but is not active against strains which express one of the other two variants i.e. there is intra-variant cross-protection, but not inter-variant cross-protection. For maximum cross-strain efficacy, therefore, the invention uses mixture comprising different variants of NMB 1870. 129-. (canceled)30: A method for raising an antibody response in a mammal , comprising administering a composition comprising an aluminum salt adjuvant , a histidine buffer , and consisting of two purified antigens , wherein the two purified antigens are selected from the group consisting of: (a) a first purified protein , comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 24; (b) a second purified protein , comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 33; and (c) a third purified protein , comprising an amino acid sequence having at least 85% identity to SEQ ID NO: 41 , wherein: the first purified protein has less than 70% sequence identity to the second purified protein; the first purified protein has less than 70% sequence identity to the third purified protein; and the second purified protein has less than 70% sequence identity to the third purified protein.31: The method of claim 30 , wherein the method protects a mammal against a Neisserial infection.3233-. (canceled)34: An immunogenic composition selected from the group consisting of:(1) a composition comprising an aluminum salt adjuvant, a histidine buffer, and consisting of two purified antigens, wherein the two purified antigens are ...

IMMUNOGENIC COMPOSITIONS

Chimeric capsular polysaccharides, conjugates comprising such chimeric capsular polysaccharides, and pharmaceutical compositions thereof. Further aspects include methods for immunising a subject against infection by administration of such polysaccharides, conjugates, or compositions. 1Streptococcus agalactiaeStreptococcus agalactiae. A chimeric bacterial capsular polysaccharide comprising at least one repeating unit of a first (GBS) capsular polysaccharide serotype and at least one repeating unit of a second (GBS) capsular polysaccharide serotype , wherein the repeating units are joined by a glycosidic bond.2. The chimeric bacterial capsular polysaccharide of which further comprises at least one repeating unit of a third GBS capsular polysaccharide serotype.3. The chimeric bacterial capsular polysaccharide of wherein the first GBS capsular polysaccharide serotype is type Ia and the second GBS capsular polysaccharide serotype is type Ib.4. The chimeric bacterial capsular polysaccharide of claim 2 , wherein the first GBS capsular polysaccharide serotype is type Ia claim 2 , the second GBS capsular polysaccharide serotype is type Ib claim 2 , and the third GBS capsular polysaccharide serotype is type III.5. The chimeric bacterial capsular polysaccharide of wherein the first GBS capsular polysaccharide serotype is type V and the second GBS capsular polysaccharide serotype is type IX.6. The chimeric bacterial capsular polysaccharide of claim 2 , wherein the first GBS capsular polysaccharide serotype is type V claim 2 , the second GBS capsular polysaccharide serotype is type IX claim 2 , and the third GBS capsular polysaccharide serotype is type VII.7. The chimeric bacterial capsular polysaccharide of wherein the ratio of the repeating units of the first and second GBS capsular polysaccharide serotypes is 1:1.8. A conjugate comprising (i) the chimeric capsular polysaccharide of and (ii) a carrier protein.9. The conjugate of claim 8 , wherein the carrier protein is ...

IMMUNOGENIC COMPOSITIONS

A method of immunization against Group B Streptococcus infection, using an immunogenic composition conjugates of GBS capsular saccharide conjugated to carrier proteins. 1Streptococcus agalactiae,. A method for immunizing a human patient against infection by comprising administering to the patient a human unit dose of an immunogenic composition comprising:(a) a first conjugate that is a capsular saccharide from Streptococcus agalactiae (GBS) serotype Ia conjugated to a first carrier protein, wherein the first carrier protein is CRM197;(b) a second conjugate that is a capsular saccharide from GBS serotype Ib conjugated to a second carrier protein, wherein the second carrier protein is CRM197; and(c) a third conjugate that is a capsular saccharide from GBS serotype III conjugated to a third carrier protein, wherein the third carrier protein is CRM197,wherein (i) each GBS capsular saccharide is present at an amount of about 5 μg, 10 μg, or 20 μg per human unit dose of the immunogenic composition and (ii) the immunogenic composition does not contain an adjuvant.2. The method of claim 1 , wherein the the patient is a female of child-bearing age.3. The method of claim 2 , wherein the patient is pregnant. This Application is filed pursuant to 35 U.S.C. § 111(a) as a U.S. Divisional Application which claims priority from U.S. application Ser. No. 14/662,429, filed Mar. 19, 2015 as a Continuation Application of U.S. application Ser. No. 13/824,041, filed Jun. 10, 2013 pursuant to 35 U.S.C. § 371 as a U.S. National Phase Application of International Patent Application Serial No. PCT/IB2011/054069, filed Sep. 16, 2011, which claims priority to U.S. Provisional Application Ser. No. 61/383,668, filed on Sep. 16, 2010; and to United Kingdom Patent Application Serial No. 1101665.6, filed Jan. 31, 2011, and the entire contents of each of the foregoing applications are hereby incorporated by reference.This application incorporates by reference the contents of 1 108 kb text file ...

COMPOSITIONS AND USES

The present invention relates to immunogenic compositions and methods for producing them, and in particular, immunogenic compositions comprising a protein antigen cross linked to an oxoadenine adjuvant. 1. An immunogenic composition comprising a 1 methyl butoxy oxoadenine compound having a piperidinyl substituent , the oxoadenine being covalently linked to an antigen.2. The immunogenic composition according to wherein 2 claim 1 , 3 claim 1 , 4 claim 1 , 5 claim 1 , 6 claim 1 , 7 claim 1 , 8 claim 1 , 9 or 10 oxoedenines are covalently linked to each antigen molecule.3. The immunogenic composition of - wherein the piperidinyl substituent is a 4-piperidnyl substituent8. An immunogenic composition of - wherein the oxoadenine molecule is linked to the antigen via a crosslinking agent and wherein the crosslinking agent is a hydrophillic compound.9. An immunogenic composition of - wherein the crosslinking agent to the oxoadenine increases the aqueous solubility of the oxoadenine compared to the solubility in the absence of the crosslinking agent.10. An immunogenic composition of - wherein the activated oxoadenine is more water soluble than an inactivated oxoadenine.11. An immunogenic composition of - wherein the increased aqueous solubility of the activated oxoadenine provided by the crosslinking agent decreases the amount of undesired agregate in antigen-adjuvant conjugate composition claim 1 , compared to activated oxoadenine no exhibiting increased soluability.12. An immunogenic composition of - wherein the crosslinking agent linked to the oxoadenine is a charged compound.13. The immunogenic composition of wherein the crosslinking agent linked to the oxoadenine is Traut's reagent or GMBS14. An immunogenic composition of wherein the crosslinking agent linked to the oxoadenine is Traut's reagent reacted with GMBS15. An immunogenic composition of - wherein the crosslinking agent is a Hetero-Bifunctional Crosslinker.16. An immunogenic composition of - further comprising a ...

MULTIPLE VARIANTS OF MENINGOCOCCAL PROTEIN NMB1870

Meningococcal protein NMB 1870 has been described in the prior art. The inventors have found that NMB 1870 is an effective antigen for eliciting anti-meningococcal antibody responses, and that it is expressed across all meningococcal serogroups. Forty-two different NMB 1870 sequences have been identified, and these group into three variants. Serum raised against a given variant is bactericidal within the same variant group, but is not active against strains which express one of the other two variants i.e. there is intra-variant cross-protection, but not inter-variant cross-protection. For maximum cross-strain efficacy, therefore, the invention uses mixture comprising different variants of NMB 1870. 1. (canceled)2. A composition comprising an aluminum salt adjuvant , a histidine buffer , and consisting of two purified antigens , wherein the two purified antigens are selected from the group consisting of:(a) a first purified protein, comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 24;(b) a second purified protein, comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 33; and(c) a third purified protein, comprising an amino acid sequence having at least 85% identity to SEQ ID NO: 41, wherein: the first purified protein has less than 70% sequence identity to the second purified protein; the first purified protein has less than 70% sequence identity to the third purified protein; and the second purified protein has less than 70% sequence identity to the third purified protein.3. The composition of claim 2 , wherein one or both of the purified proteins is a lipoprotein.4. The composition of claim 2 , wherein at least one of the two purified proteins does not include the amino acid sequence TRSKP (SEQ ID NO: 70) or TRSKPV (SEQ ID NO: 71) within 10 amino acids of its N-terminus.5. The composition of claim 2 , wherein at least one of the two purified proteins does not include the amino acid sequence ...

MODIFIED CARRIER PROTEINS FOR O-LINKED GLYCOSYLATION

Carrier proteins modified to incorporate one or more pilin glycotags and applications thereof for O-linked glycosylation are provided. In particular, a modified carrier protein comprising a carrier protein that comprises at least one GlycoTag, wherein the at least one GlycoTag is a PglL GlycoTag (NgGlycoTag), PglL GlycoTag (NlGlycoTag), or GlycoTag (NsGlycoTag), or combinations thereof is provided, together with nucleic acids and vectors encoding the modified carrier protein, host cells comprising these modofoed carrier proteins or nucleic acids encoding them, bioconjugates, methods of making bioconjugates and uses of the bioconjugates. 124-. (canceled)25Neisseria gonorrhoeaeNeisseria lactamicaNeisseria shayeganii. A modified carrier protein comprising a carrier protein that comprises at least one GlycoTag , wherein the at least one GlycoTag is a PglL GlycoTag (NgGlycoTag) , PglL GlycoTag (NlGlycoTag) , or GlycoTag (NsGlycoTag) , or combinations thereof.26. The modified carrier protein of claim 25 , wherein the at least one NgGlycoTag consists of a peptide sequence that is 12 to 30 amino acids long and comprises therein the sequence SEQ ID NO: 147.27. The modified carrier protein of claim 25 , wherein the at least one NlGlycoTag consists of a peptide sequence that is 12 to 35 amino acids long and comprises therein the sequence SEQ ID NO: 151.28. The modified carrier protein of claim 25 , wherein the at least one NsGlycoTag consists of a peptide sequence that is 12 to 31 amino acids long and comprises therein the sequence SEQ ID NO: 164.29Neisseria meningitidis. A modified carrier protein comprising a carrier protein that comprises at least one GlycoTag claim 25 , wherein the at least one GlycoTag is a PglL GlycoTag (NmGlycoTag) consisting of a peptide sequence that is 12 to 19 amino acids long and comprises therein the sequence SEQ ID NO: 142.30Pseudomonas aeruginosaC. jejuniE. coliPseudomonas aeruginosa. The modified carrier protein of claim 25 , wherein the ...

IMMUNISATION OF LARGE MAMMALS WITH LOW DOSES OF RNA

Provided is RNA encoding an immunogen is delivered to a large mammal at a dose of from 5 μg to 100 μg or at a dose between 0.1 μg per kilogram body mass of the large mammal and 1.5 μg per kilogram body mass of the large mammal. Provided is a method of raising an immune response in a large mammal, comprising administering to the large mammal a dose of from 5 μg to 100 μg or a dose of between 0.1 μg of RNA encoding the immunogen per kilogram body mass of the large mammal and 1.5 μg of RNA encoding the immunogen per kilogram body mass of the large mammal. The delivered RNA can elicit an immune response in the large mammal. 1. A method of eliciting an immune response in a large mammal , the method comprising administering to the large mammal a unit dose comprising a composition comprising lipid particles and messenger ribonucleic acid (mRNA) molecules; the mRNA molecules comprising a sequence that encodes an immunogen; the unit dose comprising between 2 μg and 100 μg of the mRNA molecules; the lipid particles comprising a first phospholipid , a polyethylene glycol-ylated (PEGylated) phospholipid , cholesterol , and a cationic lipid; the cationic lipid comprising a tertiary amine; the first phospholipid comprising an anionic phospholipid or a zwitterionic phospholipid; the lipid particles encapsulating at least half of the mRNA molecules; the large mammal being a human , horse , cattle , or pig.2. A method of eliciting an immune response in a large mammal , the method comprising administering to the large mammal a unit dose comprising a composition comprising lipid particles and mRNA molecules; the mRNA molecules comprising a sequence that encodes an immunogen; the unit dose comprising between 0.1 μg and 1.5 μg of the mRNA molecules per kg of the body mass of the large mammal; the lipid particles comprising a first phospholipid , a PEGylated phospholipid , cholesterol , and a cationic lipid; the cationic lipid comprising a tertiary amine; the first phospholipid ...

CAPSULAR POLYSACCHARIDE SOLUBILISATION AND COMBINATION VACCINES

Precipitated bacterial capsular polysaccharides can be efficiently re-solubilised using alcohols as solvents. The invention provides a process for purifying a bacterial capsular polysaccharide, comprising the steps of (a) precipitation of said polysaccharide, followed by (b) solubilisation of the precipitated polysaccharide using ethanol. CTAB can be used for step (a). The material obtained, preferably following hydrolysis and sizing, can be conjugated to a carrier protein and formulated as a vaccine. Also, in vaccines comprising saccharides from both serogroups A and C, the invention provides that the ratio (w/w) of Men A saccharide: MenC saccharide is >1. 163-. (canceled)64N. meningitidisN. meningitidisN. meningitidisN. meningitidisN. meningitidis: An immunogenic composition comprising capsular saccharides from (a) at least serogroup A of (MenA) and serogroup C of (MenC) , wherein the ratio of MenA:MenC is greater than 1 , wherein the MenA and MenC capsular saccharides are conjugated to carrier proteins , and/or (b) serogroup Y of (MenY) and one or both of serogroup C of (MenC) and serogroup W135 of (MenW135) , wherein MenY:MenW135 is greater than 1 , and/or MenY:MenC is less than 1 and wherein the MenY capsular saccharides are conjugated to carrier proteins.65: The composition of claim 64 , wherein the capsular saccharides are oligosaccharides.66: The composition of claim 65 , wherein the composition comprises MenC capsular saccharides and MenY capsular saccharides.67: The composition of claim 65 , wherein the composition comprises MenC capsular saccharides claim 65 , MenW135 capsular saccharides claim 65 , and MenY capsular saccharides.68: The composition of claim 65 , wherein the composition comprises MenA capsular saccharides claim 65 , MenC capsular saccharides claim 65 , MenW135 capsular saccharides claim 65 , and MenY capsular saccharides.69: The composition of claim 68 , wherein the ratios (w/w) for the capsular saccharides from MenA:MenC:MenW135:MenY are: ...

HETEROLOGOUS PRIME BOOST VACCINE COMPOSITIONS AND METHODS

Simian adenoviral vectors and RNA molecules, each encoding an immunogen of interest, can be sequentially administered to provide potent and long-lasting immunity. 1. A method of inducing an immune response to an infectious disease in a mammal comprisinga. administering a priming vaccine comprising an immunologically effective amount of one or more antigens encoded by either an adenoviral vector or an RNA molecule andb. administering a booster vaccine comprising an immunologically effective amount of one or more antigens encoded by either an adenoviral vector or an RNA molecule,wherein if the priming vaccine is encoded by an adenoviral vector the booster vaccine is encoded by an RNA molecule, and if the priming vaccine is encoded by an RNA molecule the booster vaccine is encoded by an adenoviral vector.2. The method of wherein the priming vaccine comprises an immunologically effective amount of one or more antigens encoded by an adenoviral vector and the boosting vaccine comprises an immunologically effective amount of one or more antigens encoded by an RIA molecule.3. The method of wherein the priming vaccine comprises an immunologically effective amount of one or more antigens encoded by an RNA molecule and the boosting vaccine comprises an immunologically effective amount of one or more antigens encoded by an adenoviral vector.4. The method of wherein the one or more antigens are from the same pathogenic organism.5. The method of wherein the one or more antigens are the same in the priming vaccine and the boosting vaccine.6. The method of wherein at least one of the epitopes of the one or more antigens are different in the priming and the boosting vaccine.7. The method of wherein the adenoviral vector is a simian adenoviral vector.8. The method of wherein the simian adenoviral vector is selected from a chimpanzee claim 7 , bonobo claim 7 , rhesus macaque claim 7 , orangutan and gorilla vector.9. The method of wherein the simian adenoviral vector is a chimpanzee ...

NEISSERIAL ANTIGENIC PEPTIDES

This invention provides, among other things, proteins, polypeptides, and fragments thereof, derived from the bacteria B. Also provided are nucleic acids encoding for such proteins, polypeptides, and/or fragments, as well as nucleic acids complementary thereto e.g., antisense nucleic acids). Additionally, this invention provides antibodies which bind to the proteins, polypeptides, and/or fragments. This invention further provides expression vectors useful for making the proteins, polypeptides, and/or fragments, as well as host cells transformed with such vectors. This invention also provides compositions of the proteins, polypeptides, fragments, and/or nucleic acids, for use as vaccines, diagnostic reagents, immunogenic compositions, and the like. Methods of making the compositions and methods of treatment with the compositions are also provided. This invention also provides methods of detecting the proteins, polypeptides, fragments, and/or nucleic acids. 1. (canceled)2. A composition comprising an adjuvant and an isolated polypeptide including the amino acid sequence selected from SEQ ID NO: 11072 and SEQ ID NO: 24053.3. The composition of claim 2 , wherein the polypeptide does not comprise the full length protein sequence of SEQ ID NO: 41367 claim 2 , SEQ ID NO: 41369 claim 2 , or SEQ ID NO: 41371.4. The composition of claim 2 , wherein the amino acid sequence of SEQ ID NO: 11072 is an antigenic fragment of SEQ ID NO: 41369; or the amino acid sequence of SEQ ID NO: 24053 is an antigenic fragment of SEQ ID NO: 41371.5. The composition of claim 4 , wherein the polypeptide does not comprise the full length protein sequence of SEQ ID NO: 41367 claim 4 , SEQ ID NO: 41369 claim 4 , or SEQ ID NO: 41371.6. The composition of claim 2 , further comprising a pharmaceutically acceptable excipient or carrier.7. The composition of claim 6 , wherein the adjuvant comprises an aluminum phosphate adjuvant.8. The composition of claim 3 , further comprising a pharmaceutically ...

DELIVERY OF RNA TO DIFFERENT CELL TYPES

RNA encoding an immunogen is co-delivered to non-immune cells at the site of delivery and also to immune cells which infiltrate the site of delivery. The responses of these two cell types to the same delivered RNA lead to two different effects, which interact to produce a strong immune response against the immunogen. The non-immune cells translate the RNA and express the immunogen. Infiltrating immune cells respond to the RNA by expressing type I interferons and pro-inflammatory cytokines which produce a local adjuvant effect which acts on the immunogen-expressing non-immune cells to upregulate major histocompatibility complex expression, thereby increasing presentation of the translated protein to T cells. The effects on the immune and non-immune cells can be achieved by a single delivery of a single RNA e.g. by a single injection. 1. A method of raising an immune response in a vertebrate , comprising administering an immunogen-encoding RNA to a delivery site in a vertebrate and then permitting immune cells to infiltrate the delivery site , such that the RNA separately enters both (a) non-immune cells at the delivery site and (b) the infiltrating immune cells , provided that the RNA includes no modified nucleotides.2. The method of claim 1 , wherein the delivery site is in skeletal muscle tissue.3. The method of claim 1 , wherein the RNA is administered by injection.4. The method of claim 3 , wherein injection is via a needle.5. The method of claim 1 , wherein the non-immune cells comprise muscle cells and/or fibroblasts.6. The method of claim 1 , wherein the RNA is translated by the non-immune cells.7. The method of any preceding claim 1 , wherein the immune cells comprise macrophages claim 1 , dendritic cells and/or monocytes.8. The method of claim 1 , wherein the immune cells are TLR7-positive.9. The method of claim 1 , wherein the RNA causes the immune cells to secrete type I interferons and/or pro-inflammatory cytokines.10. The method of claim 1 , wherein the ...

Immunisation of large mammals with low doses of rna

RNA encoding an immunogen is delivered to a large mammal at a dose of between 2 μg and 100 μg. Thus the invention provides a method of raising an immune response in a large mammal, comprising administering to the mammal a dose of between 2 μg and 100 μg of immunogen-encoding RNA. Similarly, RNA encoding and immunogen can be delivered to a large mammal at a dose of 3 ng/kg to 150 ng/kg. The delivered RNA can elicit an immune response in the large mammal.

NOVEL ADENOVIRUS

There is provided adenoviral vectors encoding a mycobacterial antigen derived from a chimp adenovirus, and to related aspects. 195-. (canceled)96. An immunogenic composition for generating a T cell response in a subject , the immunogenic composition comprising:a first composition to be administered to the subject including a recombinant adenovirus comprising a polynucleotide comprising:(a) a first polynucleotide which encodes a polypeptide having the amino acid sequence according to SEQ ID NO: 1,(b) a second polynucleotide which encodes a polypeptide having the amino acid sequence according to SEQ ID NO: 5,(c) a third polynucleotide which encodes a polypeptide having the amino acid sequence according to SEQ ID NO: 3, and(d) a fourth polynucleotide which encodes a mycobacterial Rv1196 antigen consisting of the amino acid sequence of SEQ ID NO:68, wherein the fourth polynucleotide is operatively linked to one or more sequences which direct expression of said mycobacterial Rv1196 antigen in a host cell.97. The immunogenic composition of claim 96 , further comprising: (a) a non-adenoviral vector or a non-viral vector; or', '(b) a protein., 'a second composition to be administered after the first composition, said second composition including a further component comprising98. The immunogenic composition of claim 97 , wherein the second composition includes a protein comprising the mycobacterial Rv1196 antigen.99. The immunogenic composition of claim 96 , further comprising the first composition and a pharmaceutically acceptable excipient.100. The immunogenic composition of claim 97 , further comprising the second composition and a pharmaceutically acceptable excipient.101. The immunogenic composition of claim 96 , wherein the recombinant adenovirus is replication-incompetent.102. The adenovirus of claim 96 , further comprising a fifth polynucleotide that consists of the amino acid sequence of SEQ ID NO: 70 and encodes a mycobacterial antigen.103. The adenovirus of claim ...

REGIMENS FOR IMMUNISATION WITH MENINGOCOCCAL CONJUGATES

Multivalent meningococcal conjugate vaccines are administered according to a schedule in which a first dose is administered to a patient aged between 0 and 12 months, and a second dose is administered to the patient aged between 12 and 24 months. 1. A kit comprising: (a) a multivalent meningococcal capsular saccharide-carrier protein conjugate vaccine; and (b) instructions for administering the vaccine according to a schedule that includes: (a) first administering the vaccine to a patient when said patient is about 6 months of age; and (b) then administering the vaccine to the patient when said patient is about 12 months of age , wherein the multivalent meningococcal capsular saccharide-carrier protein conjugate vaccine includes capsular saccharide-carrier protein conjugates of at least meningococcal serogroups A , C , W135 and Y.2. The kit of claim 1 , wherein the carrier protein is selected from diphtheria toxoid and CRM197.3. The kit of claim 1 , wherein the multivalent meningococcal capsular saccharide-carrier protein conjugate vaccine is unadjuvanted.4. The kit of claim 1 , wherein the multivalent meningococcal capsular saccharide-carrier protein conjugate vaccine is adjuvanted.5. The kit of claim 1 , wherein the schedule includes: (a) first administering the vaccine to a patient when said patient is 6 months of age.6. The kit of claim 1 , wherein the schedule includes: (b) administering the vaccine to the patient when said patient is about 12 months of age.7. The kit of claim 1 , wherein the schedule includes: (a) first administering the vaccine to a patient when said patient is 6 months of age; and (b) then administering the vaccine to the patient when said patient is 12 months of age. This application is a Divisional of U.S. application Ser. No. 16/716,638 filed on Dec. 17, 2019, which is a Continuation of U.S. application Ser. No. 12/225,501 filed on May 18, 2009 (now U.S. Pat. No. 10,543,265 issued Jan. 28, 2020), which is a U.S. National Phase of PCT/ ...

SIMIAN ADENOVIRUS NUCLEIC ACID-AND AMINO ACID-SEQUENCES, VECTORS CONTAINING SAME, AND USES THEREOF

The present invention relates to novel adenovirus strains with an improved seroprevalence. In one aspect, the present invention relates to isolated polypeptides of adenoviral capsid proteins such as hexon, penton and fiber protein and fragments thereof and polynucleotides encoding the same. Also provided is a vector comprising the isolated polynucleotide according to the invention and adenoviruses comprising the isolated polynucleotides or polypeptides according to the invention and a pharmaceutical composition comprising said vector, adenovirus, polypeptide and/or polynucleotide. The invention also relates to the use of the isolated polypeptides, the isolated polypeptides, the vector, the adenoviruses and/or the pharmaceutical composition for the therapy or prophylaxis of a disease. 123.-. (canceled)24. A recombinant adenoviral vector encoding a heterologous hexon protein comprising a polynucleotide that encodes an adenoviral hexon protein , wherein the polynucleotide is selected from the group consisting of:(a) a polynucleotide encoding a polypeptide having the amino acid sequence of SEQ ID NO:22;(b) a polynucleotide encoding a polypeptide having the amino acid sequence of SEQ ID NO:22, wherein the polypeptide comprises a deletion, insertion or substitution of not more than 35 amino acid residues; and(c) a polynucleotide encoding a polypeptide having an amino acid sequence which is at least 96.5% identical over its entire length to the amino acid sequence of SEQ ID NO:54.252. The recombinant adenoviral vector of claim further comprising at least one of the following:(a) an adenoviral 5′-end or an adenoviral 5′ inverted terminal repeat;(b) an adenoviral E1a region or a fragment thereof selected from the group consisting of 13S region, 12S region, and 9S region;(c) an adenoviral E1b region or a fragment thereof selected from the group consisting of small T region, large T region, and IX region;(d) an adenoviral E2b region or a fragment thereof selected from the ...

MUTANT STAPHYLOCOCCAL ANTIGENS

Mutant protein A of (SpA) with decreased affinity for the Fcγ portion of human IgG is provided. 1. An antigen comprising an amino acid sequence consisting of SEQ ID NO: 50 wherein the dipeptide at positions 60 and 61 is not QQ.2. An antigen according to claim 1 , which antigen comprises an amino acid sequence consisting of SEQ ID NO: 49 wherein the dipeptide at positions 60 and 61 is not QQ.3. An antigen according to claim 1 , which comprises more than one copy of said amino acid sequence consisting of SEQ ID NO: 50 wherein the dipeptide at positions 60 and 61 is not QQ.4. An antigen according to claim 1 , wherein the antigen elicits antibodies in a mammal that recognise SEQ ID NO: 43 or SEQ ID NO: 54.5. An antigen according to to which has decreased affinity claim 1 , relative to unmodified Staphylococcal protein A (SpA) having SEQ ID NO:43 claim 1 , for the Fcγ portion of human IgG.6. An antigen according to which has decreased affinity claim 5 , relative to unmodified SpA having SEQ ID NO:43 claim 5 , for the Fab portion of V3-containing human B cell receptors.7. An antigen according to comprising SEQ ID NO :43 claim 1 , wherein at least one amino acid selected from position 43 claim 1 , 44 claim 1 , 70 claim 1 , 71 claim 1 , 96 claim 1 , 97 claim 1 , 104 claim 1 , 105 claim 1 , 131 claim 1 , 132 claim 1 , 162 claim 1 , 163 claim 1 , 190 claim 1 , 191 claim 1 , 220 claim 1 , 221 claim 1 , 247 claim 1 , 248 claim 1 , 278 claim 1 , 279 claim 1 , 305 and 306 of SEQ ID NO: 43 is mutated.8. An antigen according to claim 1 , comprising a sequence selected from SEQ ID NO:51 claim 1 , SEQ ID NO: 52 claim 1 , SEQ ID NO: 47 and SEQ ID NO: 48.9. A fusion protein comprising an antigen according to and another protein.10. An immunogenic composition comprising an antigen according to .11. The composition according to claim 10 , wherein the composition also comprises an adjuvant.12. The composition according to claim 11 , wherein said adjuvant is selected from the group ...

Vaccines for neisseria gonorrhoeae

Methods and compositions for immunizing a human subject against Neisseria gonorrhoeae.

Novel compositions and methods

The present invention is directed to a polypeptide which comprises: (i) an Rv2386c protein sequence; (ii) a variant of an Rv2386c protein sequence; of (iii) an immunogenic fragment of an Rv2386c protein sequence. In other aspects the invention is directed to associated polynucleotides, fusion proteins and methods for the treatment or prevention of tuberculosis.

Immunogenic composition

The present application discloses an immunogenic composition comprising at least 2 different N. meningitidis capsular saccharides, wherein one or more is/are selected from a first group consisting of MenA, MenC, MenY and MenW which is/are conjugated through a linker to a carrier protein(s), and one or more different saccharides is/are selected from a second group consisting of MenA, MenC, MenY and MenW which is/are directly conjugated to a carrier protein(s).

HEPATITIS B IMMUNISATION REGIMEN AND COMPOSITIONS

There is provided a method of treating chronic hepatitis B infection (CHB) in a human, comprising the steps of: 1. A method of treating chronic hepatitis B infection (CHB) in a human , comprising the steps of:a) administering to the human a composition comprising a replication-defective chimpanzee adenoviral (ChAd) vector comprising a polynucleotide encoding a hepatitis B surface antigen (HBs) and a nucleic acid encoding a hepatitis B virus core antigen (HBc);b) administering to the human a composition comprising a Modified Vaccinia Virus Ankara (MVA) vector comprising a polynucleotide encoding a hepatitis B surface antigen (HBs) and a nucleic acid encoding a hepatitis B virus core antigen (HBc); andc) administering to the human a composition comprising a recombinant hepatitis B surface antigen (HBs), a recombinant hepatitis B virus core antigen (HBc) and an adjuvant.2. The method according to claim 1 , wherein the steps of the method are carried out sequentially claim 1 , with step a) preceding step b) and step b) preceding step c).3. The method according to claim 2 , wherein step c) of the method is repeated.4. The method according to claim 2 , or in which the period of time between each step is 1 week claim 2 , 2 weeks claim 2 , 4 weeks claim 2 , 6 weeks 8 weeks claim 2 , 12 weeks claim 2 , 6 months or 12 months claim 2 , for example 4 weeks or 8 weeks.5. The method according to claim 1 , wherein step c) is carried out concomitantly with step a) and/or with step b).6. A method of treating chronic hepatitis B infection (CHB) in a human claim 1 , comprising the steps of:a) administering to the human i) a composition comprising a replication-defective chimpanzee adenoviral (ChAd) vector comprising a polynucleotide encoding a hepatitis B surface antigen (HBs) and a nucleic acid encoding a hepatitis B virus core antigen (HBc) and, concomitantly, ii) a composition comprising a recombinant hepatitis B surface antigen (HBs), a recombinant hepatitis B virus core antigen ( ...

MYCOBACTERIUM ANTIGENIC COMPOSITION

Immunogenic compositions comprising an M72 related antigen, wherein the conductivity of the composition is 13 mS/cm or lower, or the concentration of salts of the composition is 130 mM or lower, and their use in medicine, are provided. 1. An immunogenic composition comprising an M72 related antigen , whereinthe concentration of salts in said composition is 130 mM or lower.2. The immunogenic composition according to claim 1 , wherein the conductivity of the composition is 10 mS/cm or lower.3. The immunogenic composition according to claim 2 , wherein the conductivity of the composition is 3 mS/cm or lower.4. The immunogenic composition according to claim 1 , wherein the concentration of salts in said composition is 100 mM or lower.5. The immunogenic composition according to claim 4 , wherein the concentration of salts in said composition is 40 mM or lower.6. The immunogenic composition according to claim 1 , wherein the concentration of sodium chloride in said composition is 100 mM or lower.7. The immunogenic composition according to claim 6 , wherein the concentration of sodium chloride in said composition is 40 mM or lower.8. The immunogenic composition according to claim 1 , wherein the concentration of CaClin the immunogenic composition is 30 mM or lower.9. The immunogenic composition according to claim 1 , wherein the concentration of MgSOin the immunogenic composition is 60 or lower.10. The immunogenic composition according to claim 1 , total concentration of NH claim 1 , Mg and Ca ions is 40 mM or lower.11. The immunogenic composition according to claim 1 , further comprising a non-ionic tonicity agent.12. The immunogenic composition according to claim 11 , wherein the non-ionic tonicity agent is a polyol.13. The immunogenic composition according to claim 12 , wherein the polyol is sorbitol.14. The immunogenic composition according to claim 13 , wherein the concentration of sorbitol is between about 4 and about 6% (w/v).15. The immunogenic composition ...

Immunogenic liposomal formulation

A liposomal composition comprising a liposome and an aminoalkansulfonic buffer is described and claimed.

STAPHYLOCOCCUS AUREUS TYPE 8 CAPSULAR SACCHARIDES

The invention provides a method for releasing capsular polysaccharide from type 5 or type 8 cells, comprising the step of treating the cells with acid. The invention further provides a process for purifying capsular polysaccharide from type 5 or type 8 cells comprising this method. Other processing steps may be included in the process, such as enzymatic treatment, e.g. to remove nucleic acid, protein and/or peptidoglycan contaminants; diafiltration, e.g. to remove low molecular weight contaminants; anion exchange chromatography, e.g. to remove residual protein; and concentration. 126-. (canceled)27S. aureus. A composition comprising an type 8 capsular polysaccharide obtainable by a process comprising the step of treating the cells with acid , wherein the acid treatment results in the capsular polysaccharide having a degree of O-acetylation between 60-100%.28S. aureus. The composition of further comprising one or more protein antigen(s) selected from the group consisting of a clfA antigen; a clfB antigen; a sdrE2 antigen; a sdrC antigen; a sasF antigen; a emp antigen; a sdrD antigen; a spa antigen; a esaC antigen; a esxA antigen; a esxB antigen; a sta006 antigen; a isdC antigen; a Ma antigen; a sta011 antigen; a isdA antigen; a isdB antigen; and a sta073 antigen.29S. aureus. The composition of claim 27 , wherein the composition comprises protein antigens according to one of combinations (1) to (10) below:(1) a esxA antigen, a esxB antigen, a sta006 antigen and a Hla antigen;(2) a esxA antigen, a esxB antigen, a sta006 antigen and a sta011 antigen;(3) a esxA antigen, a esxB antigen and a sta011 antigen;(4) a esxA antigen, a esxB antigen, a Hla antigen, a sta006 antigen and a sta011 antigen;(5) a esxA antigen, a esxB antigen and a Hla antigen;(6) a Hla antigen, a sta006 antigen and a sta011 antigen;(7) a esxA antigen and a esxB antigen;(8) a esxA antigen, a esxB antigen and a sta006 antigen;(9) a esxA antigen, a esxB antigen, a sta011 antigen and a sta073 antigen; and( ...

PROCESS FOR THE MANIPULATION OF NUCLEIC ACIDS

The present invention discloses a process for engineering a host cell comprising the steps of; a) integrating a first polynucleotide cassette including a first selection marker flanked by a first pair of recombination sites; b) removing the first selection marker by the action of a recombinase which recognises the first pair of recombination sites; c) integrating a second polynucleotide cassette including a second selection marker flanked by a second pair of recombination sites; and d) removing the second selection marker by the action of a recombinase which recognises the second pair of recombination sites. Also disclosed is a host cell genome polynucleotide comprising a first recombinantly engineered region and a second recombinantly engineered region, wherein a first single recombination site is adjacent to the first recombinantly engineered region, and a second single recombination site is adjacent to the second recombinantly engineered region. 125.-. (canceled)26. A method of removing at least two portions of insert nucleic acid from a genomic polynucleotide in a host cell , said method comprising the steps of:a) preparing the genomic polynucleotide comprising a first insert nucleic acid which is flanked by a pair of first recombination sites in the same orientation which are identical to each other and have a first nucleic acid sequence;b) exposing the genomic polynucleotide of step a) to a recombinase that recognises the first recombination sites such that the identical recombination sites recombine resulting in the excision of the first insert nucleic acid and one of the first recombination sites;c) inserting into the genomic polynucleotide of step b) a second insert nucleic acid flanked by a pair of second recombination sites in the same orientation wherein the second recombination sites are identical to each other and have a second nucleic acid sequence which shares 70-98% sequence identity with the first nucleic acid sequence; andd) exposing the genomic ...

IMMUNOGENIC COMPOSITION

The present invention discloses modified ClfA proteins that contain glycosylation site consensus sequences. The invention also discloses a conjugate comprising a modified ClfA protein and an antigen (for example a saccharide antigen), wherein the antigen is linked (either directly or through a linker) to an amino acid residue of the modified ClfA protein. 1. A polypeptide comprising an amino acid sequence of SEQ ID NO. 3 or an amino acid sequence at least 80% , 85% , 90% , 92% , 95% , 96% , 97% , 98% or 99% identical to SEQ ID NO. 3 , modified in that the amino acid sequence comprises one or more consensus sequence(s) selected from: D/E-X-N-Z-S/T (SEQ ID NO. 21) and K-D/E-X-N-Z-S/T-K (SEQ ID NO. 22) , wherein X and Z are independently any amino acid apart from proline; wherein said consensus sequence has been added at , or substituted for , one or more amino acids between amino acid residues 313-340 of SEQ ID NO: 3 or at an equivalent position within an amino acid sequence at least 80% , 85% , 90% , 92% , 95% , 96% , 97% , 98% or 99% identical to SEQ ID NO. 3.2. The polypeptide of claim 1 , wherein said consensus sequence has been substituted for amino acid residue Q327 claim 1 , D329 claim 1 , P331 or I337 in SEQ ID NO. 3 claim 1 , or substituted in an amino acid sequence at least 80% claim 1 , 85% claim 1 , 90% claim 1 , 92% claim 1 , 95% claim 1 , 96% claim 1 , 97% claim 1 , 98% or 99% identical to SEQ ID NO. 3 at an amino acid position equivalent to amino acid residue Q327 claim 1 , D329 claim 1 , or I337 in SEQ ID NO. 3.3. (canceled)4. (canceled)5. The polypeptide of claim 1 , wherein the amino acid sequence further comprises at least one amino acid substitution selected from P116 to S and Y118 to A with reference to the amino acid sequence of SEQ ID NO. 3 (or an equivalent position in an amino acid sequence at least 80% claim 1 , 85% claim 1 , 90% claim 1 , 92% claim 1 , 95% claim 1 , 96% claim 1 , 97% claim 1 , 98% or 99% identical to SEQ ID NO. 3) claim 1 , ...

IMMUNIGENIC ALPHA-BRANCHED TREHALOSE-DIESTERS

The invention relates to compounds of formula (I) and their use in eliciting a pro-Thl7 immune response. Further provided are methods of production of said compounds. (Formula I) wherein m is an integer between 4 and 13; n is an integer between 4 and 13; x is an integer between 4 and 13; y is an integer between 4 and 13. 257.-. (canceled)58. The compound according to claim 1 , wherein m is 6 and n is 6.59. The compound according to claim 1 , wherein x is 6 and y is 6.60. The compound according to claim 1 , wherein m is 6 claim 1 , n is 6 claim 1 , x is 6 and y is 6 claim 1 , or a pharmaceutically acceptable salt and/or solvate thereof.62. The method according to claim 61 , wherein the pro-Th17 response involves the elicitation of TNF-alpha claim 61 , IL-6 claim 61 , IL-23 and IL-1beta.63. The method according to claim 61 , wherein the pro-Th17 response involves the elicitation of IL-17 cytokine.64. The method according to claim 61 , wherein the pro-Th17 response involves the elicitation of Th17 cells.65. The method of claim 61 , wherein the subject is a human subject.66. The method according to claim 61 , wherein m is 5 claim 61 , 6 claim 61 , or 7; n is 5 claim 61 , 6 claim 61 , or 7; x is 5 claim 61 , 6 claim 61 , or 7; and y is 5 claim 61 , 6 claim 61 , or 7.67. The method according to claim 61 , wherein m is 6 claim 61 , n is 6 claim 61 , x is 6 and y is 6.69. The immunogenic composition according to claim 68 , wherein m is 6 and n is 6.70. The immunogenic composition according to claim 68 , wherein x is 6 and y is 6.71. The immunogenic composition according to claim 68 , wherein m is 6 claim 68 , n is 6 claim 68 , x is 6 and y is 6.72. The immunogenic composition according to claim 68 , wherein antigen is from a human or non-human bacterial claim 68 , viral claim 68 , fungal claim 68 , microorganism or multicellular parasitic pathogen.73Mycobacterium tuberculosis.. The immunogenic composition according to claim 72 , wherein antigen is from74. The immunogenic ...

Immunogenic rhinovirus peptides

Fusion proteins comprising a carrier protein and a Human Rhinovirus (HRV) peptide, and immunogenic compositions containing such fusion proteins.

OUTER MEMBRANE VESICLE (OMV) VACCINE COMPRISING N. MENINGITIDIS SEROGROUP B OUTER MEMBRANE PROTEINS

A composition comprising (a) serogroup B outer membrane vesicles (OMVs), and (b) an immunogenic component selected from other proteins, or immunogenic fragments thereof. Component (b) preferably includes a protein from a different NmB strain from that from which the OMV of component (a) is derived. The OMVs are preferably obtained by deoxycholate extraction. Optionally, the composition may also comprise a protective antigen against other pathogens. 1. (canceled)2. A method of inducing a bactericidal immune response in an animal , comprising administering to the animal a composition which comprises(a) an immunologically effective amount of an isolated protein comprising an amino acid sequence having at least 95% identity to the mature form of SEQ ID NO: 2536 of WO99/57280 or an immunogenic fragment comprising twenty or more consecutive amino acids of the mature form of the amino acid sequence of SEQ ID NO: 2536 of WO99/57280; and{'i': 'Neisseria meningitidis', '(b) a outer membrane preparation comprising an immunologically effective amount of PorA.'}3Neisseria meningitidis. The method according to claim 2 , wherein the outer membrane preparation consists of an immunologically effective amount of PorA.4Neisseria meningitidis. The method according to claim 2 , wherein the immune response induced by the isolated protein is bactericidal against at least three strains of in the mammal.5. The method according to claim 2 , wherein the isolated protein is a recombinant protein.6. The method according to claim 2 , wherein the isolated protein is expressed as a fusion protein.7Neisseria meningitidis. The method according to claim 2 , wherein the isolated protein and the PorA protein are from different strains of8. The method according to claim 2 , wherein the composition further comprises a pharmaceutically acceptable carrier claim 2 , adjuvant claim 2 , diluent or buffer.9. The method according to claim 2 , wherein the composition further comprises aluminum hydroxide.10. The ...

Compositions and methods for protein glycosylation

Described herein are oligosaccharyl transferases for use in N-glycosylating proteins of interest in vitro and in host cells. Methods for using such oligosaccharyl transferases, nucleic acids encoding such oligosaccharyl transferases, and host cells comprising such oligosaccharyl transferases are also provided herein. Glycoconjugates generated by using such oligosaccharyl transferases are also provided herein.

Heterologous expression of neisserial proteins

Alternative and improved approaches to the heterologous expression of the proteins of Neisseria meningitidis and Neisseria gonorrhoeae are disclosed. These approaches typically affect the level of expression, the ease of purification, the cellular localization, and/or the immunological properties of the expressed protein.

Heterologous expression of neisserial proteins

Alternative and improved approaches to the heterologous expression of the proteins of Neisseria meningitidis and Neisseria gonorrhoeae are disclosed. These approaches typically affect the level of expression, the ease of purification, the cellular localization, and/or the immunological properties of the expressed protein.

DELIVERY OF RNA TO TRIGGER MULTIPLE IMMUNE PATHWAYS

RNA encoding an immunogen is co-delivered to non-immune cells at the site of delivery and also to immune cells which infiltrate the site of delivery. The responses of these two cell types to the same delivered RNA lead to two different effects, which interact to produce a strong immune response against the immunogen. The non-immune cells translate the RNA and express the immunogen. Infiltrating immune cells respond to the RNA by expressing type I interferons and pro-inflammatory cytokines which produce a local adjuvant effect which acts on the immunogen-expressing non-immune cells to upregulate major histocompatibility complex expression, thereby increasing presentation of the translated protein to T cells. The effects on the immune and non-immune cells can be achieved by a single delivery of a single RNA e.g. by a single injection. 1. A method of raising an immune response in a vertebrate , comprising administering an immunogen-encoding RNA to the vertebrate such that the RNA: (i) stimulates an endosomal innate immunity receptor; (ii) stimulates a cytoplasmic innate immunity receptor , and (iii) is translated to provide expression of the immunogen , provided that the RNA includes no modified nucleotides.2. The method of claim 1 , wherein the RNA is administered to skeletal muscle tissue.3. The method of claim 1 , wherein the RNA is administered by injection.4. The method of claim 3 , wherein injection is via a needle.5. The method of claim 1 , wherein the endosomal innate immunity receptor is TLR7.6. The method of claim 1 , wherein the cytoplasmic innate immunity receptor is a RNA helicase.7. The method of claim 1 , wherein the RNA is administered in combination with a delivery system.8. The method of claim 7 , wherein the delivery systems comprises: (i) liposomes; (ii) non-toxic and biodegradable polymer microparticles; and/or (iii) a submicron cationic oil-in-water emulsion.9. The method of claim 1 , wherein the RNA is +-stranded.10. The method of claim 1 , ...

IMMUNOGENIC COMPOSITION

The present invention discloses a recombinant bacteriophage comprising a phage genome polynucleotide including a gene encoding a heterologous antigen protein(s) and a killing gene encoding a protein that is capable of killing a host bacterium. Such a recombinant bacteriophage is designed to prime a subject's immune response and to kill the bacterium that it infects such that the “prime and kill” bacteriophage provides two lines of protection against infectious disease. 169-. (canceled)70. A recombinant bacteriophage comprising a phage genome polynucleotide including a gene encoding a heterologous antigen protein(s) and a killing gene encoding a protein that is capable of killing a host bacterium wherein following entry of the recombinant bacteriophage into a host bacterium , expression of the heterologous antigen protein is driven by a promoter allowing the heterologous antigen to be released from the host bacterium and the heterologous antigen protein(s) is not expressed as part of a phage coat/capsid protein.71. The recombinant bacteriophage of claim 70 , wherein the recombinant bacteriophage is adapted to bind to a host bacterium through modification of a gene encoding a bacteriophage tail fibre/plate and insert the phage genome polynucleotide into said host bacterium.72Shigella, Pseudomonas, Propionibacterium, AcinetobacterE. coli, P. aeruginosa, C. difficile, P. acnes, K. pneumoniae, N. gonorrhoea. The recombinant bacteriophage of claim 70 , wherein the host bacterium is a staphylococcal claim 70 , streptococcal claim 70 , claim 70 , meningococcal claim 70 , bacterium.73. The recombinant bacteriophage of claim 70 , wherein the gene encoding the heterologous antigen protein is under the control of an early promoter or a strong promoter.74. The recombinant bacteriophage claim 70 , wherein the killing gene is under the control of a late or a weak promoter.75. The recombinant bacteriophage of claim 70 , wherein the bacteriophage is selected from the group of ...

IN-VITRO POTENCY ASSAY FOR PROTEIN-BASED MENINGOCOCCAL VACCINES

The invention uses ELISA or similar assays for analysing a meningococcal vaccine. The assay uses antibodies which bind to meningococcal proteins within the vaccine, and in particular monoclonal antibodies which are bactericidal for meningococcus and/or which recognise conformational epitopes within the meningococcal proteins. By performing the assay on a series of dilutions of a test vaccine, and by comparing the results with those obtained using a reference vaccine of known potency, it is possible to determine the relative potency of the test vaccine. This value can be used as a parameter for determining whether a manufactured batch of a vaccine is suitable for release to the public, or whether it has experienced a production failure and so should not be used.

CHLAMYDIA ANTIGENS

The invention provides antigens for use in the treatment, prevention and/or diagnosis of infection. In particular, the invention provides antigens CT733, CT153, CT601, CT279, CT443, CT372, CT456, CT381, CT255, CT341, CT716, CT745, CT387, CT812, CT869, CT166, CT175, CT163, CT214, CT721, CT127, CT043, CT823 and/or CT600 from for the treatment, prevention or diagnosis of infection. 1. A protein comprising the amino acid sequence of any one of SEQ ID NO: 2 , SEQ ID NO:4 , SEQ ID NO:6 , SEQ ID NO:8 , SEQ ID NO:10 , SEQ ID NO:12 , SEQ ID NO:14 , SEQ ID NO:16 , SEQ ID NO: 18 , SEQ ID NO:40 , SEQ ID NO:42 , SEQ ID NO:44 , SEQ ID NO:46 , SEQ ID NO: 48 , SEQ ID NO:50 , SEQ ID NO:52 , SEQ ID NO:54 , SEQ ID NO:136 or SEQ ID NO:140 for use in therapy or diagnosis.2. A protein having 50% or greater sequence identity to a protein according to .3. A protein comprising a fragment of the amino acid sequence of .4. A protein according to claim 3 , wherein the fragment comprises at least 8 consecutive amino acids of the amino acid sequence of SEQ ID NO: 2 claim 3 , SEQ ID NO:4 claim 3 , SEQ ID NO:6 claim 3 , SEQ ID NO:8 claim 3 , SEQ ID NO:10 claim 3 , SEQ ID NO:12 claim 3 , SEQ ID NO:14 claim 3 , SEQ ID NO:16 claim 3 , SEQ ID NO: 18 claim 3 , SEQ ID NO:40 claim 3 , SEQ ID NO:42 claim 3 , SEQ ID NO:44 claim 3 , SEQ ID NO:46 claim 3 , SEQ ID NO: 48 claim 3 , SEQ ID NO:50 claim 3 , SEQ ID NO:52 claim 3 , SEQ ID NO:54 claim 3 , SEQ ID NO:136 or SEQ ID NO:140.5. An antibody which binds to a protein according to for use in therapy or diagnosis.6. A nucleic acid molecule which encodes a protein or antibody according to for use in therapy or diagnosis.7. A nucleic acid molecule according to claim 6 , comprising the nucleotide sequence of any one of SEQ ID NO: 1 claim 6 , SEQ ID NO:3 claim 6 , SEQ ID NO:5 claim 6 , SEQ ID NO:7 claim 6 , SEQ ID NO:9 claim 6 , SEQ ID NO:11 claim 6 , SEQ ID NO:13 claim 6 , SEQ ID NO:15 claim 6 , SEQ ID NO:17 claim 6 , SEQ ID NO:39 claim 6 , SEQ ID NO:41 claim 6 , ...

CATIONIC OIL-IN-WATER EMULSIONS

This invention generally relates to cationic oil-in-water emulsions that contain high concentrations of cationic lipids and have a defined oil:lipid ratio. The cationic lipid can interact with the negatively charged molecule thereby anchoring the molecule to the emulsion particles. The cationic emulsions described herein are useful for delivering negatively charged molecules, such as nucleic acid molecules to cells, and for formulating nucleic acid-based vaccines. 143-. (canceled)44. A method for preparing a composition comprising an RNA molecule complexed with a particle of a cationic oil-in-water emulsion , comprising: a. the ratio of oil:lipid (mole:mole) in the oil-in-water emulsion is at least about 8:1 (mole:mole),', 'b. the concentration of cationic lipid in said composition is at least about 1.25 mM, and', 'c. the cationic lipid is not DC-Cholesterol;, '(i) providing an oil-in-water emulsion comprising particles that are dispersed in an aqueous continuous phase, wherein the average diameter of said particles is from about 80 nm to about 150 nm; wherein the average diameter does not change by more than 10% when the emulsion is stored at 4° C. for one month; wherein the emulsion comprises an oil and a cationic lipid, and wherein(ii) providing an aqueous solution comprising the RNA molecule; and(iii) combining the oil-in-water emulsion of (i) and the aqueous solution of (ii), thereby preparing the composition.45. The method of claim 44 , wherein the cationic oil-in-water emulsion of (i) and RNA solution of (ii) are combined at about 1:1 (v/v) ratio.46. The method of claim 44 , wherein the aqueous solution comprising the RNA molecule comprises a salt.47. The method of claim 46 , wherein the salt is NaCl.48. The method of claim 47 , wherein the aqueous solution comprises about 20 mM NaCl.49. The method of claim 44 , wherein the aqueous solution comprising the RNA molecule is a buffer.50. The method of claim 49 , wherein the buffer is a citrate buffer.51. The ...

IMIDAZOQUINOLINE DERIVATIVES AND THEIR USE IN THERAPY

This invention relates inter alia to novel imidazoquinoline derivatives and their use in therapy, particularly as vaccine adjuvants. 2. The compound according to wherein Rrepresents H claim 1 , C-Calkyl or C-CalkoxyC-Calkyl.3. The compound according to wherein Rrepresents H claim 2 , C-Calkyl or C-CalkoxyC-Calkyl;4. The compound according to wherein Rrepresents H claim 3 , n-butyl or CHCHOCH—.5. The compound according to wherein Rrepresents H.6. The compound according to wherein Rrepresents n-butyl.7. The compound according to wherein Rrepresents CHCHOCH—.8. The compound according to wherein Rrepresents C-Calkylene-OH.9. The compound according to wherein Rrepresents —CHCHOH.10. The compound according to wherein Rrepresents C-Calkylene-OH.11. The compound according to wherein Rrepresents —CHCHOH.12. The compound according to wherein q represents an integer 1 to 3.13. The compound according to wherein q represents 1.14. The compound according to wherein q represents 3.15. The compound according to wherein q represents an integer 1 to 3.16. The compound according to wherein q represents 1.17. The compound according to wherein q represents 3.18. The compound according to wherein q represents an integer 1 to 3.19. The compound according to wherein q represents 1.20. The compound according to wherein q represents 3. This application is a Divisional of copending U.S. application Ser. No. 16/330,599, filed on Mar. 5, 2019, which is a National Stage Entry of PCT International Application No. PCT/EP2017/072152 filed on Sep. 5, 2017, which claims the benefit under 35 U.S.C. § 119(e) to U.S. Provisional Application No. 62/384,618, filed on Sep. 7, 2016, all of which are hereby expressly incorporated by reference into the present application.This invention was made with Government support under contract #HHSN272200900036C awarded by the National Institutes of Health. The Government has certain rights in the invention.The present invention relates to novel imidazoquinoline ...

IMIDAZOQUINOLINE DERIVATIVES AND THEIR USE IN THERAPY

This invention relates inter alia to novel imidazoquinoline derivatives and their use in therapy, particularly as vaccine adjuvants. 2. The compound according to wherein Rrepresents H claim 1 , C-Calkyl or C-Calkoxy C-Calkyl.3. The compound according to wherein Rrepresents H claim 2 , C-Calkyl or C-Calkoxy C-Calkyl;4. The compound according to wherein Rrepresents H claim 3 , n-butyl or CHCHOCH—.5. The compound according to wherein Rrepresents H.6. The compound according to wherein Rrepresents n-butyl.7. The compound according to wherein Rrepresents CHCHOCH—.8. The compound according to wherein Rrepresents C-Calkylene-OH.9. The compound according to wherein Rrepresents —CHCHOH.10. The compound according to wherein Rrepresents C-Calkylene-OH.11. The compound according to wherein Rrepresents —CHCHOH.12. The compound according to wherein q represents an integer 1 to 3.13. The compound according to wherein q represents 1.14. The compound according to wherein q represents 3.15. The compound according to wherein q represents an integer 1 to 3.16. The compound according to wherein q represents 1.17. The compound according to wherein q represents 3.18. The compound according to wherein q represents an integer 1 to 3.19. The compound according to wherein q represents 1.20. The compound according to wherein q represents 3. This application is a Divisional of copending U.S. application Ser. No. 16/330,599, filed on Mar. 5, 2019, which is a National Stage Entry of PCT International Application No. PCT/EP2017/072152 filed on Sep. 5, 2017, which claims the benefit under 35 U.S.C. § 119(e) to U.S. Provisional Application No. 62/384,618, filed on Sep. 7, 2016, all of which are hereby expressly incorporated by reference into the present application.This invention was made with Government support under contract # HHSN272200900036C awarded by the National Institutes of Health. The Government has certain rights in the invention.The present invention relates to novel imidazoquinoline ...

NOVEL METHODS FOR INDUCING AN IMMUNE RESPONSE

The present invention relates to methods for inducing an immune response, in particular methods for adjuvanting the immune response to an antigen comprising the separate administration of a saponin and a TLR4 agonist. 2. A method for inducing an immune response in a subject using a TLR4 agonist and a saponin , said method comprising the steps:(i) administering to the subject the TLR4 agonist;(ii) administering to the subject the saponin;3. A kit comprising:(i) a first composition comprising a TLR4 agonist; and(ii) a second composition comprising a saponin.4. The kit according to claim 3 , further comprising an antigen claim 3 , wherein an antigen is present within the first and/or second compositions.5. The kit according to comprising:(i) a first composition comprising a TLR4 agonist;(ii) a second composition comprising a saponin; and(iii) a third composition comprising an antigen.6. A multi-chamber syringe comprising a first compartment and a second compartment claim 3 , said first compartment comprising a first composition comprising a TLR4 agonist and said second compartment comprising a second composition comprising a saponin claim 3 , said first and second compositions being administrable to a subject either sequentially or concurrently.7. The method of claim 1 , wherein the TLR4 agonist is a non-toxic derivative of lipid A.8. The method of claim 7 , wherein the TLR4 agonist is 3-de-O-acylated monophosphoryl lipid A.9. The method of claim 1 , wherein the saponin is QS21.10. The method of claim 1 , wherein the TLR4 agonist is 3-de-O-acylated monophosphoryl lipid A and the saponin is QS2I.11. The method of claim 1 , wherein the amount of TLR4 agonist in a single adult human dose is 1 to 100 ug and the amount of saponin in a single adult human dose is 1 to 100 ug.12. The method of claim 1 , wherein the TLR4 agonist and saponin are administered to locations less than 10 cm apart.13. The method of claim 1 , wherein the TLR4 agonist and saponin are administered to a ...

COMBINATION VACCINES WITH SEROGROUP B MENINGOCOCCUS AND D/T/P

Serogroup B meningococcus antigens can successfully be combined with diphtheria, tetanus and pertussis toxoids (“DTP”) to provide effective combination vaccines for protecting against multiple pathogens. These combinations are effective with a range of different adjuvants, and with both pediatric-type and booster-type DTP ratios. The adjuvant can improve the immune response which the composition elicits; alternatively, by including an adjuvant it is possible for the compositions to have a relatively lower amount of antigen while nevertheless having immunogenicity which is comparable to unadjuvanted combination vaccines. 1: An immunogenic composition , comprising: (a) a serogroup B meningococcus immunogen; and (b) a diphtheria toxoid , a tetanus toxoid , and a pertussis toxoid , wherein the diphtheria toxoid is present in an excess relative to tetanus toxoid as measured in Lf units.2: The composition of claim 1 , further comprising an adjuvant. This application is a Divisional of U.S. application Ser. No. 14/420,238, with an international filing date of Sep. 6, 2013, now U.S. Pat. No. 9,526,776; which is the National Phase of PCT Application No. PCT/EP2013/068414, filed Sep. 6, 2013; which claims the benefit of U.S. Provisional Application No. 61/697,756, filed Sep. 6, 2012; all of which are incorporated herein by reference in their entirety.The content of the following submission on ASCII text file is incorporated herein by reference in its entirety: a computer readable form (CRF) of the Sequence Listing (file name: 303822012710SeqList.txt, date recorded: Dec. 16, 2016, size: 122 KB).This invention is in the field of combination vaccines i.e. vaccines containing mixed immunogens from more than one pathogen, such that administration of the vaccine can simultaneously immunize a subject against more than one pathogen.Vaccines containing antigens from more than one pathogenic organism within a single dose are known as “multivalent” or “combination” vaccines. Various ...

IMMUNOGENIC BACTERIAL VESICLES WITH OUTER MEMBRANE PROTEINS

Knockout of the meningococcal mltA homolog gives bacteria that spontaneously release vesicles that are rich in immunogenic outer membrane proteins and that can elicit cross-protective antibody responses with higher bactericidal titres than OMVs prepared by normal production processes. Thus the invention provides a bacterium having a knockout mutation of its mltA gene. The invention also provides a bacterium, wherein the bacterium: (i) has a cell wall that includes peptidoglycan; and (ii) does not express a protein having the lytic transglycosylase activity MltA protein. The invention also provides compositions comprising vesicles that, during culture of bacteria of the invention, are released into the culture medium. 110-. (canceled)11Neisseria: A process for preparing bacterial vesicles , comprising the steps of: (i) culturing a bacterium in a culture medium such that the bacterium releases vesicles into said medium; and (ii) collecting the vesicles from said medium , wherein: (a) the bacterium has a knockout mutation of its mltA gene; and (b) the bacterium has a knockout mutation of its siaA gene.12N. meningitidis.: The process of claim 11 , wherein the bacterium is13N. meningitidis: The process of claim 12 , wherein the is from serogroup A claim 12 , B claim 12 , C claim 12 , W135 or Y.14: The process of claim 11 , further comprising a step of formulating the vesicles released by said bacterium into a vaccine composition.15Escherichia: A process for preparing bacterial vesicles claim 11 , comprising the steps of: (i) culturing an bacterium in a culture medium such that the bacterium releases vesicles into said medium; and (ii) collecting the vesicles from said medium claim 11 , wherein: (a) the bacterium has a cell wall that includes peptidoglycan; and (b) the bacterium does not express a protein having the lytic transglycosylase activity of MltA protein.16: The process of claim 15 , wherein the bacterium also has a knockout mutation of at least one further gene. ...

FERMENTATION PROCESS

The present invention relates to processes for fermentation and virulence factor production, especially PT production, for large scale manufacturing. More particularly, processes including a medium conditioning step carried out prior to inoculation. 128.-. (canceled)29. A process for producing a conditioned growth medium comprising:a. providing a sterile growth medium;b. holding the sterile growth medium at a temperature between about 28 and about 35° C. for about 20 to 35 hours; and{'sup': −1', '−1, 'c. stirring and/or aerating the sterile growth medium to produce an oxygen volumetric mass transfer coefficient (kLa) of about 10 hto about 130 h, thereby providing the conditioned growth medium.'}30. The process of claim 29 , wherein step b) is carried out at a temperature between about 29° C. and about 33° C. claim 29 , about 30° C. and about 32° C. claim 29 , or about 31° C.; and/orwherein step b) is carried out for about 25 to 35 hours, about 30 to 35 hours, or about 32 hours.31. The process of claim 29 , wherein in step c) the sterile growth medium is stirred continuously for the duration of step b) claim 29 , optionally{'sup': −1', '−1', '−1, 'wherein the stirring is at a stirring speed that produces an oxygen volumetric mass transfer coefficient (kLa) of about 60 hto about 130 h, or about 90 h; and/or'}wherein in step c) the sterile growth medium is aerated continuously for the duration of step b), optionally{'sup': −1', '−1', '−1, 'wherein the aerating is at a flow rate that produces an oxygen volumetric mass transfer coefficient (kLa) of about 60 hto about 130 h, or about 90 h; and/or'}wherein step c) comprises stirring and aerating the sterile growth medium continuously for the duration of step b), optionally{'sup': −1', '−1', '−1, 'wherein the stirring and aerating are at a stirring speed and flow rate that produces an oxygen volumetric mass transfer coefficient (kLa) of about 60 hto about 130 hor about 90 h.'}32. The process of claim 29 , wherein the ...

IMMUNOGENIC COMPOSITION FOR USE IN THERAPY

This application relates to immunogenic compositions comprising a Type 5 capsular saccharide conjugated to a carrier protein to form a Type 5 capsular saccharide conjugate. 1Staphylococcus aureus. A method of immunising against infection comprising a step of administering to a human patient a single dose of an immunogenic composition comprising:{'i': Staphylococcus aureus', 'S. aureus', 'S. aureus, '(a) a Type 5 capsular saccharide conjugated to a carrier protein to form a Type 5 capsular saccharide conjugate, wherein the Type 5 capsular saccharide conjugate is administered at a saccharide dose of 3-50 μg;'}{'i': Staphylococcus aureus', 'S. aureus', 'S. aureus, '(b) a Type 8 capsular saccharide conjugated to a carrier protein to form a Type 5 capsular saccharide conjugate, wherein the Type 8 capsular saccharide conjugate is administered at a saccharide dose of 3-50 μg; and'}(c) a ClfA polypeptide comprising an amino acid sequence at least 90% identical to SEQ ID NO: 7.2. (canceled)3S. aureus. The method of wherein the Type 5 capsular saccharide has a molecular weight of over 25 kDa.4S. aureus. The method of wherein the Type 8 capsular saccharide has a molecular weight of over 25 kDa.5S. aureusS. aureus. The method of wherein the Type 5 capsular saccharide and/or the Type 8 capsular saccharide is 50-100% O-acetylated.6S. aureus. The method of wherein the ratio of polysaccharide to protein in the Type 5 capsular saccharide conjugate is between 1:5 and 5:1 (w:w).7S. aureus. The method of wherein the ratio of polysaccharide to protein in the Type 8 capsular saccharide conjugate is between 1:5 and 5:1 (w:w).8S. aureusS. aureus. The method wherein the same saccharide dose of Type 5 capsular saccharide and Type 8 capsular saccharide is present in the immunogenic composition.912-. (canceled)13. The method of wherein the single dose of the immunogenic composition is administered 5-50 days before a planned hospital procedure.14S. aureusS. aureus. The method of wherein the ...

Uses of parasite macrophage migration inhibitory factors

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

SIMIAN ADENOVIRUS NUCLEIC ACID-AND AMINO ACID-SEQUENCES, VECTORS CONTAINING SAME, AND USES THEREOF

The present invention relates to novel adenovirus strains with an improved seroprevalence. In one aspect, the present invention relates to isolated polypeptides of adenoviral capsid proteins such as hexon, penton and fiber protein and fragments thereof and polynucleotides encoding the same. Also provided is a vector comprising the isolated polynucleotide according to the invention and adenoviruses comprising the isolated polynucleotides or polypeptides according to the invention and a pharmaceutical composition comprising said vector, adenovirus, polypeptide and/or polynucleotide. The invention also relates to the use of the isolated polynucleotides, the isolated polypeptides, the vector, the adenoviruses and/or the pharmaceutical composition for the therapy or prophylaxis of a disease. 123.-claim . (canceled)25. The recombinant adenoviral vector of claim 24 , wherein the E4 region of the vector comprises ORF6 from a human adenovirus.26. The recombinant adenoviral vector of claim 25 , wherein the E4 region of the vector comprises ORF6 from human adenovirus 5 (Ad5 E4ORF6).27. The recombinant adenoviral vector of further comprising at least one of the following:(a) an adenoviral 5′-end or an adenoviral 5′ inverted terminal repeat;(b) an adenoviral E1a region or a fragment thereof selected from the group consisting of 13S region, 12S region, and 9S region;(c) an adenoviral E1b region or a fragment thereof selected from the group consisting of small T region, large T region, and IX region;(d) an adenoviral E2b region or a fragment thereof selected from the group consisting of small pTP region, Polymerase region, and IVa2 region;(e) an adenoviral L1 region or a fragment thereof encoding an adenoviral protein selected from the group consisting of 28.1 kD protein, polymerase, agnoprotein, 52/55 kDa protein, and IIIa protein; a VII protein,', 'a V protein, and', 'a Mu protein;, '(f) an adenoviral L2 region or a fragment thereof encoding an adenoviral protein selected from ...

IMMUNOGENIC COMPOSITION

The present invention relates to immunogenic compositions comprising 26 μg-45 μg of pneumolysin and/or PhtD, vaccines comprising the immunogenic compositions and their use in medicine. 1. An immunogenic composition comprising 26 μg-45 μg , 26 μg-40 μg , 28 μg-35 μg or around 30 μg of detoxified pneumolysin (dPly) and/or PhtD (polyhistidine triad family D) , per human dose.2. The immunogenic composition of wherein the pneumolysin has been chemically detoxified.3. The immunogenic composition of wherein the pneumolysin has been genetically detoxified.43. The immunogenic composition of any one of - wherein the PhtD (poly histidine triad family D) comprises an amino acid sequence at least 85% claims 1 , 90% claims 1 , 95% claims 1 , 98% claims 1 , 99% or 100% identical to the sequence of amino acids 21-838 of Sequence ID No. 4 of WO00/37105.515-. (canceled)16. The immunogenic composition of any preceding claim wherein the immunogenic composition does not comprise an oil in water adjuvant.1719-. (canceled)20Streptococcus pneumoniae. The immunogenic composition of any preceding claim wherein the immunogenic composition further comprises 1 or more (e.g. 7 claims 1 , 8 claims 1 , 9 claims 1 , 10 claims 1 , 11 claims 1 , 12 claims 1 , 13 claims 1 , 14 claims 1 , 15 claims 1 , 16 claims 1 , 17 claims 1 , 18 claims 1 , 19 claims 1 , 20 claims 1 , 21 claims 1 , 22 claims 1 , or 23) capsular saccharide conjugates.21Streptococcus pneumoniae. The immunogenic composition of wherein the 1 or more capsular saccharide conjugates comprises a conjugated serotype 4 saccharide claim 20 , a conjugated serotype 6B saccharide claim 20 , a conjugated serotype 9V saccharide claim 20 , a conjugated serotype 14 saccharide claim 20 , a conjugated serotype 18C saccharide claim 20 , a conjugated serotype 19F saccharide and a conjugated serotype 23F saccharide.22Streptococcus pneumoniae. The immunogenic composition of or wherein the 1 or more capsular saccharide conjugates comprises a conjugated ...

Novel influenza antigens

The present invention relates to novel influenza antigens, novel immunogenic or vaccine compositions, as well as to uses of and to methods for producing said antigens and compositions. In particular, the invention relates to recombinant forms of hemagglutinin (HA) and their use in vaccine compositions for the prevention of influenza virus infections.

ADJUVANTING MENINGOCOCCAL FACTOR H BINDING PROTEIN

Factor H binding protein (fHBP) has been proposed for use in immunising against serogroup B meningococcus (‘MenB’). This antigen can be efficiently adsorbed to an aluminium hydroxyphosphate adjuvant by (i) ensuring that adsorption takes place at a pH which is equal to or below the adjuvant's point of zero charge (PZC), and/or (ii) selecting a fHBP and adjuvant with an isoelectric point/PZC within the range of 5.0 to 7, and/or (iii) selecting a fHBP with an isoelectric point above the adjuvant's PZC and using a buffer to bring the pH to within 1.2 pH units of the PZC. The adsorption is particularly useful for compositions which include multiple fHBP variants, and also in situations where an aluminium hydroxide adjuvant should be avoided. Buffered pharmaceutical compositions can include at least two different meningococcal fHBP antigens, both of which are at least 85% adsorbed to aluminium hydroxyphosphate adjuvant. 1. A buffered immunogenic composition comprising at least two different meningococcal fHBP antigens , both of which are at least 85% adsorbed to aluminium hydroxyphosphate adjuvant.2. The composition of claim 1 , wherein (i) each of the two different fHBP antigens has an isoelectric point between 5.0 and 7.0 claim 1 , and (ii) the aluminium hydroxyphosphate adjuvant has a point of zero charge between 5.0 and 7.0.3. The composition of claim 2 , wherein the pH of the buffered composition is in the range of 5.0 to 7.0.4. An immunogenic composition comprising two different meningococcal fHBP antigens claim 2 , both of which are adsorbed to aluminium hydroxyphosphate adjuvant claim 2 , wherein (i) both of the meningococcal fHBP antigens have an isoelectric point between 5.0 and 7.0 claim 2 , and (ii) the aluminium hydroxyphosphate adjuvant has a point of zero charge between 5.0 and 7.0.5. A buffered immunogenic composition comprising two different meningococcal fHBP antigens claim 2 , both adsorbed to aluminium hydroxyphosphate adjuvant claim 2 , wherein (i) ...

LIPOSOMES HAVING USEFUL N:P RATIO FOR DELIVERY OF RNA MOLECULES

Nucleic acid immunisation is achieved by delivering a RNA encapsulated within a liposome comprising a cationic lipid, wherein the liposome and the RNA have a N:P ratio of between 1:1 and 20:1. 115.-. (canceled)16. A method for raising a protective immune response in a vertebrate , comprising the step of administering to the vertebrate an effective amount of a liposome comprising a cationic lipid and the liposome and RNA have a N:P ratio of between 1:1 and 20:1.17. A method for raising a protective immune response in a vertebrate , comprising the step of administering to the vertebrate an effective amount of a pharmaceutical composition comprising a liposome wherein the liposome comprises a cationic lipid and the liposome and RNA have a N:P ratio of between 1:1 and 20:1.18. The method of claim 16 , wherein the vertebrate is a human or a veterinary mammal.19. The method of claim 16 , wherein the RNA is self-replicating.20. The method of claim 19 , wherein the self-replicating RNA encodes (i) a RNA-dependent RNA polymerase which can transcribe RNA from the self-replicating RNA molecule and (ii) an immunogen.21. The method of claim 19 , wherein the self-replicating RNA has two open reading frames claim 19 , the first of which encodes an alphavirus replicase and the second of which encodes the immunogen.22. The method of claim 19 , wherein the immunogen can elicit an immune response in vivo against respiratory syncytial virus glycoprotein F.23. The method of claim 16 , wherein the immunogen may elicit an immune response against a bacterium claim 16 , virus claim 16 , fungus claim 16 , or parasite.24. The method of claim 16 , wherein the immune response may comprise an antibody response.25. The method of claim 16 , wherein the immune response may comprise a cell-mediated immune response. This application is a continuing application of U.S. patent application Ser. No. 14/130,748, filed on Jan. 3, 2014, which is a national stage entry of PCT/US2012/045829, filed Jul. 6, ...

DETECTION OF PRAME GENE EXPRESSION IN CANCER

The present invention relates to PRAME specific primers and probes, diagnostic kits and methods. The invention further relates to treatment of specific populations of cancer patients suffering from PRAME expressing tumours. 1. An oligonucleotide comprising a nucleotide sequence selected from the group consisting of SEQ ID NO:5 to 7.25-. (canceled)6. A kit comprising:(i) a forward primer comprising SEQ ID NO:5(ii) a reverse primer comprising SEQ ID NO:6; and(iii) a probe comprising SEQ ID NO:7.78-. (canceled)9. A method for determining the presence or absence of PRAME positive tumour tissue in a patient-derived biological sample , comprising the step of contacting a nucleotide sequence obtained or derived from a patient-derived biological sample with one or more components selected from the group consisting of:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(i) at least one oligonucleotide of ;'}(ii) a set of primers comprising an oligonucleotide comprising SEQ ID NO:5 and an oligonucleotide comprising SEQ ID NO:6;(iii) a probe comprising SEQ ID NO:7; and/or(iv) a forward primer comprising SEQ ID NO:5, a reverse primer comprising SEQ ID NO:6; and a probe comprising SEQ ID NO:7.10. The method of claim 9 , further comprising the step of amplifying a nucleotide sequence and detecting in the sample the amplified nucleotide sequence.11. The method of claim 10 , further comprising the step of detecting whether the nucleotide sequence hybridises to component (iii).12. The method of in which the biological sample is Formalin-Fixed claim 11 , Paraffin-Embedded tissue.13. A method of treating a patient comprising using the method of to select a patient having PRAME positive tumour tissue and then administering a PRAME immunotherapy to the patient.1419-. (canceled) The present invention relates to diagnostic methods and compositions for the detection of PRAME, as well as the immunotherapeutic treatment of populations of patients suffering from PRAME expressing tumours.PRAME ...

HEPATITIS B IMMUNISATION REGIMEN AND COMPOSITIONS

The present invention relates to immunogenic compositions and combinations thereof which may find use in immunisation regimens for the treatment of chronic hepatitis B. An immunogenic composition comprises a replication-defective chimpanzee adenoviral (ChAd) vector comprising polynucleotides encoding HBs, HBc human invariant chain (hIi) fused to the HBc. Another immunogenic composition comprises a Modified Vaccinia Virus Ankara (MVA) vector comprising polynucleotides encoding HBs and HBc. Another immunogenic composition comprises recombinant HBs, C-terminal truncated recombinant HBc and an adjuvant containing MPL and QS-21. 1. An immunogenic composition comprising a replication-defective chimpanzee adenoviral (ChAd) vector comprising a polynucleotide encoding a hepatitis B surface antigen (HBs) , a polynucleotide encoding a hepatitis B virus core antigen (HBc) and a polynucleotide encoding the human invariant chain (hIi) fused to the HBc.2. An immunogenic composition according to wherein the ChAd vector is selected from the group consisting of ChAd3 claim 1 , ChAd63 claim 1 , ChAd83 claim 1 , ChAd155 claim 1 , ChAd 157 claim 1 , Pan 5 claim 1 , Pan 6 claim 1 , Pan 7 and Pan 9.3. An immunogenic composition according to or wherein the ChAd vector is ChAd155 and comprises a polynucleotide encoding hIi claim 1 , HBc claim 1 , 2A and HBs.4. An immunogenic composition according to any one of to wherein the vector comprises polynucleotides encoding an HBc comprising SEQ ID NO:11 or an amino acid sequence at least 98% homologous thereto fused to a polynucleotide encoding an hIi comprising SEQ ID NO:7 or an amino acid sequence at least 98% homologous thereto or SEQ ID NO:12 or an amino acid sequence at least 98% homologous thereto claim 1 , and an HBs comprising SEQ ID NO:1 or an amino acid sequence at least 98% homologous thereto claim 1 , wherein the polynucleotides encoding hIi-HBc and HBs are separated by a polynucleotide encoding an amino acid sequence comprising SEQ ID ...

POXVIRAL VACCINES

The present application relates to novel administration regimens for poxviral vectors comprising nucleic acid constructs encoding antigenic proteins and invariant chains. In particular the use of said poxviral vectors for priming or for boosting an immune response is disclosed. 120-. (canceled)21. A method for stimulating an immune response comprising administering to a subject: (i) a nucleic acid sequence encoding at least one antigenic protein or antigenic fragment thereof operatively linked to', '(ii) a nucleic acid encoding at least one invariant chain; and, '(a) a Modified Vaccinia Ankara vector comprising a nucleic acid construct comprising(b) an adenoviral vector comprising a nucleic acid sequence encoding at least a second antigenic protein or antigenic fragment thereof;wherein the second antigenic protein or antigenic fragment thereof is immunologically identical to the antigenic protein or antigenic fragment thereof encoded by the nucleic acid construct comprised by the Modified Vaccinia Ankara vector.221. The method of claim , wherein the Modified Vaccinia Ankara vector (a) is used for the priming of the immune response and the adenoviral vector of (b) is used for boosting the immune response231. The method of claim , wherein the adenoviral vector of (b) is used for the priming of the immune response and the Modified Vaccinia Ankara vector (a) is used for boosting the immune response.241. The method of claim , wherein the adenoviral vector is a non-human great ape-derived adenoviral vector.254. The method of claim , wherein the non-human great ape-derived adenoviral vector is a chimpanzee or bonobo adenoviral vector.261. The method of claim , wherein the at least one antigenic protein is a protein of a pathogenic organism , cancer-specific protein , or a protein associated with an abnormal physiological response.276. The method of claim , wherein the pathogenic organism is a virus , a bacterium , a protist or a multicellular parasite.281. The method of ...

THERAPEUTIC VIRAL VACCINE

The present invention relates to viral Fc receptor or immunogenic fragments thereof for treating a viral infection in a subject and, in particular, a herpes vims infection. The present invention also relates to a heterodimer comprising or consisting of an Fc receptor from a HSV vims or an immunogenic fragment thereof and a binding partner from said HSV vims or a fragment thereof, for use in therapy. 112-. (canceled)13. A recombinant viral FcR or immunogenic fragment thereof , wherein the ability of said viral FcR or immunogenic fragment thereof to bind to a human antibody Fc domain is reduced or abolished compared to the corresponding native viral Fc receptor.14. The recombinant viral FcR or immunogenic fragment thereof of claim 13 , wherein said recombinant viral FcR or immunogenic fragment thereof is a HSV2 gE2 or immunogenic fragment thereof and wherein said HSV2 gE2 or immunogenic fragment thereof comprises a mutation or a combination of mutations with respect to the sequence shown in SEQ ID NO: 1 selected from 289 insert ADIGL; 338 insert ARAA; H245K; P317R; P319R; P319G; P319K; H245A_P319R; H245A_P319G; H245A_P319K; H245A_P319T; P319D; S338D; R320D; N241A_R320D; A248K_V340M; P318Y; A248K_V340R; A248T_V340W; A248K_V340W; A246W_R320G; A246W_P317K; A246W_R320D; A246W_R320T; V340W; A248G_V340W; H245G_R320D; P318D; A246W_P317F; P319G_V340W; A248T_V340M; P317K_V340W; V340F; V340D; H245A_R320D; P317F_V340W; A246W_P317S; H245S_R320D; R314G_P318D; A248T; P318S; P317K; P317S_V340W; H245D; R314P_V340W; R314L_318D; P319L_V340W; P317F; P318D_S338G; R314G_V340W; P317K_S338H; R314L_V340W; P318R; P318Q; P317F_S338G; R314G_P318I; H245G_P319G; P317L; P318I; A248T_F322A; H245E; P318T; P318R_S338G; P318D_S338H; P317F_S338H; A248T_V340R; A248T_F322I; H245A_R320G; P318R_S338H; H245S_R320G; P317K_S338G; A248T_F322P; V340R; R314L_P318R; H245S_R320T; R314G_P318R; R320E; H245G_R320G; H245A_R320T; A246W; P318I_S338G; P317K_V340M; P317I; R320H; R314P_P318I; P318I_S338H; P317F_V340M; ...

ADENOVIRUS POLYNUCLEOTIDES AND POLYPEPTIDES

The present invention relates to isolated polynucleotide and polypeptide sequences derived from novel chimpanzee adenovirus ChAd157, as well as to recombinant polynucleotides, vectors, adenoviruses, cells and compositions comprising said polynucleotide and polypeptide sequences. 1. An isolated polynucleotide , wherein the polynucleotide encodes a polypeptide selected from the group consisting of:(a) a polypeptide having the amino acid sequence according to SEQ ID NO: 1, and(b) a functional derivative of a polypeptide having the amino acid sequence according to SEQ ID NO: 1, wherein the functional derivative has an amino acid sequence which is at least 99.8% identical over its entire length to the amino acid sequence of SEQ ID NO: 1.2. A recombinant polynucleotide comprising a polynucleotide selected from the group consisting of:(a) a polynucleotide which encodes a polypeptide having the amino acid sequence according to SEQ ID NO: 1, and(b) a polynucleotide which encodes a functional derivative of a polypeptide having the amino acid sequence according to SEQ ID NO: 1, wherein the functional derivative has an amino acid sequence which is at least 99.8% identical over its entire length to the amino acid sequence of SEQ ID NO: 1.3. A recombinant vector comprising a polynucleotide selected from the group consisting of:(a) a polynucleotide which encodes a polypeptide having the amino acid sequence according to SEQ ID NO: 1, and(b) a polynucleotide which encodes a functional derivative of a polypeptide having the amino acid sequence according to SEQ ID NO: 1, wherein the functional derivative has an amino acid sequence which is at least 99.8% identical over its entire length to the amino acid sequence of SEQ ID NO: 1.4. A recombinant adenovirus comprising at least one polynucleotide or polypeptide selected from the group consisting of:(a) a polynucleotide which encodes a polypeptide having the amino acid sequence according to SEQ ID NO: 1,(b) a polynucleotide which encodes ...

NOVEL METHODS FOR INDUCING AN IMMUNE RESPONSE

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

EXPRESSION SYSTEM

Compositions and methods related to periplasmic expression of a toxin including diphtheria toxin or CRM197 are provided herein. 2. The process of wherein the 3′ toxin sequence encodes a polypeptide having the amino acid sequence of SEQ ID NO: 32.3. The process of wherein the 3′ toxin sequence comprises SEQ ID NO: 31.4. The process of wherein the 3′ toxin sequence encodes CRM197.5. The process of wherein the 3′ toxin sequence encodes a polypeptide having at least 95% sequence identity to SEQ ID NO: 32.6. The process of wherein the polynucleotide encodes a polypeptide comprising any one of SEQ ID NOs: 33-45.7. The process of wherein the 5′ signal sequence is directly 5′ of the 3′ toxin sequence of the polynucleotide.8. The process of wherein the 5′ signal sequence encodes a signal peptide having an amino acid sequence selected from:(a) SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, and 26;(b) variants of SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, and 26 containing 1, 2 or 3 point mutations, insertions or deletions, which variants are capable of directing transport of said bacterial toxin polypeptide to the periplasm of said bacterial host cell, and(c) fragments of at least 10 amino acids of SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, and 26, which fragments are capable of directing transport of said bacterial toxin polypeptide to the periplasm of said bacterial host cell.9. The process of wherein the 5′ signal sequence encodes a signal peptide having an amino acid sequence selected from:(i) SEQ ID NO: 24;(ii) variants of SEQ ID NO: 24 containing 1, 2 or 3 point mutations, insertions or deletions, which variants are capable of directing transport of said bacterial toxin polypeptide to the periplasm of said bacterial host cell; and(iii) fragments of at least 10 amino acids of SEQ ID NO: 24, which fragments are capable of directing transport of said bacterial toxin polypeptide to the periplasm of said bacterial host cell.10. The process of ...

Zika viral antigen constructs

Compounds useful as components of immunogenic compositions for the induction of an immunogenic response in a subject against viral infection, methods for their use in treatment, and processes for their manufacture are provided herein. The compounds comprise a nucleic acid construct comprising a sequence which encodes a Zika virus antigen. A particular embodiment is a nucleic acid-based vaccine construct encoding a polypeptide comprising a full-length Zika virus prME antigen. A particular embodiment is a self-replicating RNA molecule comprising a construct encoding a polypeptide comprising a full-length Zika virus prME antigen.

MUTANT STAPHYLOCOCCAL ANTIGENS

Mutant protein A of (SpA) with decreased affinity for the Fcγ portion of human IgG is provided. 1. An antigen comprising an amino acid sequence consisting of SEQ ID NO: 50 wherein the dipeptide at positions 60 and 61 is not QQ.2. An antigen according to claim 1 , which antigen comprises an amino acid sequence comprising or consisting of SEQ ID NO: 49 wherein the dipeptide at positions 60 and 61 is not QQ.3. An antigen according to claim 1 , which comprises more than one copy of said amino acid sequence consisting of SEQ ID NO: 50 wherein the dipeptide at positions 60 and 61 is not QQ.4. An antigen according to claim 1 , wherein the antigen elicits antibodies in a mammal that recognise SEQ ID NO: 43 or SEQ ID NO: 54.5. An antigen according to to which has decreased affinity claim 1 , relative to unmodified Staphylococcal protein A (SpA) having SEQ ID NO:43 claim 1 , for the Fcγ portion of human IgG.6. An antigen according to which has decreased affinity claim 5 , relative to unmodified SpA having SEQ ID NO:43 claim 5 , for the Fab portion of V3-containing human B cell receptors.7. An antigen according to comprising SEQ ID NO :43 claim 1 , wherein at least one amino acid selected from position 43 claim 1 , 44 claim 1 , 70 claim 1 , 71 claim 1 , 96 claim 1 , 97 claim 1 , 104 claim 1 , 105 claim 1 , 131 claim 1 , 132 claim 1 , 162 claim 1 , 163 claim 1 , 190 claim 1 , 191 claim 1 , 220 claim 1 , 221 claim 1 , 247 claim 1 , 248 claim 1 , 278 claim 1 , 279 claim 1 , 305 and/or and 306 of SEQ ID NO: 43 is mutated.8. An antigen according to claim 1 , comprising a sequence selected from SEQ ID NO:51 claim 1 , SEQ ID NO: 52 claim 1 , SEQ ID NO: 47 and SEQ ID NO: 48.9. A fusion protein comprising an antigen according to and another protein.10. An immunogenic composition comprising an antigen according to .11. The composition according to claim 10 , wherein the composition also comprises an adjuvant.12. The composition according to claim 11 , wherein said adjuvant is selected ...

COMBINATION NEISSERIAL COMPOSITIONS

Compositions comprising a first biological molecule from a bacterium and a second biological molecule from a bacterium. The term “biological molecule” includes proteins and nucleic acids. Preferred species are and 1. (canceled)2. A method of inducing a bactericidal immune response in an animal , comprising administering to the animal a composition which comprises(a) an immunologically effective amount of a protein lacking an N-terminal cysteine having at least 95% identity to the amino acid sequence of the mature form of SEQ ID NO: 3518; and{'i': 'N. meningitidis', '(b) an immunologically effective amount of an protein comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 7645.'}3. The method of claim 2 , wherein the composition consists essentially of (a) and (b).4. The method of claim 2 , wherein the composition does not further comprise a protein having an amino acid sequence of at least 80% identity to SEQ ID NO: 3516.5. The method according to claim 2 , wherein the protein lacking an N-terminal cysteine is a recombinant protein.6. The method according to claim 2 , wherein the protein lacking an N-terminal cysteine is expressed as a fusion protein.7. The method according to claim 2 , wherein the protein lacking the N-terminal cysteine is fused to a GST protein or a HIS-tag.8N. meningitidisNeisseria meningitidis.. The method according to claim 2 , wherein the protein lacking an N-terminal cysteine and the protein are from different strains of9. The method according to claim 2 , wherein the composition additionally comprises an adjuvant or buffer suitable for a medicament.10. The method according to claim 2 , wherein the composition additionally comprises an adjuvant.11. The method according to claim 2 , wherein the composition further comprises aluminum hydroxide.12Neisseria meningitidis. The method according to claim 2 , wherein the composition further comprises a third biological molecule different than (a) and (b).13. The method ...

PROCESS FOR PREPARING A COMPOSITION COMPRISING A PROTEIN D POLYPEPTIDE

The present invention relates to a process for preparing immunogenic compositions. More particularly, it relates to a process for preparing liquid compositions of Protein D polypeptide and their use in preparing immunogenic compositions comprising Protein D polypeptide which may be used in the treatment or prevention of an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in a subject, e.g. human. 1. A process for preparing a liquid composition comprising a Protein D polypeptide , wherein the Protein D polypeptide has at least identity to SEQ ID NO: 2 , wherein the process comprises mixing the Protein D polypeptide with sucrose and poloxamer.2. The process for preparing a liquid composition comprising a Protein D polypeptide according to claim 1 , wherein the process comprises mixing the Protein D polypeptide with sucrose and poloxamer prior to mixing the Protein D polypeptide with other antigens.3. The process for preparing a liquid composition comprising a Protein D polypeptide according to claim 1 , wherein the process comprises mixing the Protein D polypeptide with solution(s) comprising: (a) sucrose to a concentration of 5 to 20% (w/v) claim 1 , 10 to 20% (w/v) claim 1 , or 10 to 15% (w/v) claim 1 , and (b) poloxamer to a concentration of 0.1 to 1% (w/v) claim 1 , 0.5 to 1% (w/v) claim 1 , or 1% (w/v).4. The process for preparing a liquid composition comprising a Protein D polypeptide according to claim 1 , wherein the process comprises mixing the Protein D polypeptide with solution(s) comprising: (a) sucrose claim 1 , (b) poloxamer and (c) a salt.5. The process for preparing a liquid composition comprising a Protein D polypeptide according to claim 1 , wherein the process comprises mixing the Protein D polypeptide with solution(s) comprising: (a) sucrose claim 1 , (b) poloxamer claim 1 , (c) a salt and (d) a buffer.6. The process for preparing a liquid composition comprising a Protein D polypeptide according to claim 1 , wherein the process ...

NON-CROSS-LINKED ACELLULAR PERTUSSIS ANTIGENS FOR USE IN COMBINATION VACCINES

The present invention relates to stable compositions comprising acellular pertussis antigens that have not been cross-linked with a cross-linking agent such as formaldehyde or glutaraldehyde and their use as acellular pertussis components in combination vaccines. Processes for preparing these antigens and compositions are also disclosed. 1. A process for preparing an aP component , comprising:{'i': 'B. pertussis', 'a. growing a culture of a strain expressing a genetically detoxified pertussis toxin;'}{'i': B. pertussis', 'B. pertussis, 'b. purifying two or more antigens from the culture to obtain two or more batches each containing a different purified antigen; and'}c. mixing the two or more batches to prepare the aP component,{'i': 'B. pertussis', 'wherein the process is characterised in that the purified antigens are not treated with a cross-linking agent, and'}{'i': 'B. pertussis', 'wherein the aP component comprises at least two non-cross-linked antigens selected from PT, FHA and pertactin with the proviso that any PT is genetically detoxified.'}2. The process of claim 1 , wherein the genetically detoxified pertussis toxin is PT-9K/129G. This application is a Divisional of copending application Ser. No. 14/435,258 filed on May 4, 2015, which is the U.S. National Phase of International Application No. PCT/EP2013/071372, filed Oct. 1, 2013 and published in English, which claims the benefit of U.S. provisional patent application 61/713,356 filed Oct. 12, 2012. The complete contents of the foregoing application are incorporated herein by reference for all purposes.The present invention relates to stable compositions comprising acellular pertussis antigens that have not been cross-linked with a cross-linking agent such as formaldehyde or glutaraldehyde and their use as acellular pertussis components in combination vaccines.causes whooping cough. Pertussis antigens in vaccines are either cellular (whole cell, in the form of inactivated cells; ‘wP’) or acellular (‘aP ...

Regimens for Immunisation With Meningococcal Conjugates

Multivalent meningococcal conjugate vaccines are administered according to a schedule in which a first dose is administered to a patient aged between 0 and 12 months, and a second dose is administered to the patient aged between 12 and 24 months. 114-. (canceled)15. A method for immunizing a patient , comprising: (a) administering a multivalent meningococcal capsular saccharide-carrier protein conjugate vaccine to the patient when said patient is aged between 5 and 7 months; and (b) administering a multivalent meningococcal capsular saccharide-carrier protein conjugate vaccine to the patient when said patient is aged between 11 and 13 months , wherein the multivalent meningococcal capsular saccharide-carrier protein conjugate vaccine includes capsular saccharide-carrier protein conjugates of meningococcal serogroups A , C , W135 , and Y.16. A method for immunizing a patient who previously received a multivalent meningococcal capsular saccharide-carrier protein conjugate vaccine when said patient was aged between 5 and 7 months , comprising: administering a multivalent meningococcal capsular saccharide-carrier protein conjugate vaccine to the patient when said patient is aged between 11 and 13 months , wherein the multivalent meningococcal capsular saccharide-carrier protein conjugate vaccine includes capsular saccharide-carrier protein conjugates of at least meningococcal serogroups C and Y.17. A kit comprising: (a) a multivalent meningococcal capsular saccharide-carrier protein conjugate vaccine; and (b) instructions for administering the vaccine according to a schedule that includes: (a) first administering the vaccine to a patient when said patient is aged between 5 and 7 months; and (b) then administering the vaccine to the patient aged between 11 and 13 months , wherein the multivalent meningococcal capsular saccharide-carrier protein conjugate vaccine includes capsular saccharide-carrier protein conjugates of at least meningococcal serogroups C and Y.18. The ...

Antigen delivery platforms

This disclosure provides platforms for delivery of herpes virus proteins to cells, particularly proteins that form complexes in vivo. In some embodiments these proteins and the complexes they form elicit potent neutralizing antibodies. Thus, presentation of herpes virus proteins using the disclosed platforms permits the generation of broad and potent immune responses useful for vaccine development.

Adenovirus Polynucleotides and Polypeptides

There is provided inter alia an isolated polynucleotide, wherein the polynucleotide encodes a polypeptide selected from the group consisting of: 142-. (canceled)461. The recombinant vector according to claim , wherein the polynucleotide encodes a polypeptide having the amino acid sequence according to SEQ ID NO: 1.474. The recombinant vector according to claim , wherein the polynucleotide has a sequence according to SEQ ID NO: 2.481. The recombinant vector according to claim , wherein the polynucleotide comprises at least one of the following:(a) an adenoviral 5′-end, preferably an adenoviral 5′ inverted terminal repeat;(b) an adenoviral E1A region, or a fragment thereof selected from among the E1A_280R and E1A_243R regions;(c) an adenoviral E1B or IX region, or a fragment thereof selected from among the group consisting of the E1B_19K, E1B_55K or IX regions;(d) an adenoviral E2b region; or a fragment thereof selected from among the group consisting of the E2B_pTP, E2B_Polymerase and E2B_IVa2 regions;(e) an adenoviral L1 region, or a fragment thereof, said fragment encoding an adenoviral protein selected from the group consisting of the L1_13.6k protein, L1_52k and L1_IIIa protein;(f) an adenoviral L2 region, or a fragment thereof, said fragment encoding an adenoviral protein selected from the group consisting of the L2_penton protein, L2_pVII, L2_V, and L2_pX protein;(g) an adenoviral L3 region, or a fragment thereof, said fragment encoding an adenoviral protein selected from the group consisting of the L3_pVI protein, L3_hexon protein and L3_protease;(h) an adenoviral E2A region;(i) an adenoviral L4 region, or a fragment thereof said fragment encoding an adenoviral protein selected from the group consisting of the L4_100k protein, the L4_33k protein and protein L4_VIII;(j) an adenoviral E3 region, or a fragment thereof selected from the group consisting of E3 ORF1, E3 ORF2, E3 ORF3, E3 ORF4, E3 ORF5, E3 ORF6, E3 ORF7, E3 ORF8, and E3 ORF9;(k) an adenoviral L5 ...

LIPOSOME PRODUCTION USING ISOPROPANOL

Provided are compositions and methods for producing a lipidic film. The method comprises the steps of: (i) dissolving a lipid mix in isopropanol to form a homogeneous mix; and (ii) removing the solvent from the homogeneous mix to form a lipidic film, wherein the lipid mix comprises a lipid and cholesterol. 1. A method for producing a lipidic film comprising the steps of:(i) dissolving a lipid mix in isopropanol to form a homogeneous mix; and(ii) removing the isopropanol from the homogeneous mix to form a lipidic film,wherein the lipid mix comprises a lipid and cholesterol.2. A method for producing a lipidic film according to claim 1 , wherein the lipid mix further comprises a lipopolysaccharide.3. A method for producing a lipidic film according to claim 2 , wherein the lipopolysaccharide is MPL.4. A method for producing a lipidic film according to wherein the solvent is removed from the homogeneous mix by evaporation.5. A method for producing a lipidic film according to claim 1 , wherein the solvent is removed from the homogeneous mix by vacuum distillation.6. A method for producing liposomes comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a) producing a lipidic film according to the method of ;'}b) hydrating the lipidic film with a hydrating solution to form a coarse liposome suspension;c) reducing size of the coarse liposome suspension produced in step (b) with high shear and high pressure homogenizer to form liposomes.7. A method according to claim 6 , wherein the hydrating solution comprises a buffer.8. A method according to claim 7 , wherein the buffer is a phosphate buffer.9. A method according to claim 6 , wherein the method comprises an additional step d) sterilising the liposomes.10. (canceled)11. A liposome comprising cholesterol and isopropanol.12. An immunogenic composition comprising a liposome according to . The present invention relates to methods for the production of liposomes. In particular, the invention relates to methods for the ...

COMPOSITIONS FOR IMMUNISING AGAINST STAPHYLOCOCCUS AUREUS

An effective vaccine may require several antigenic components, and so various combinations of antigens are identified for use in immunisation. These polypeptides may optionally be used in combination with saccharides. 122-. (canceled)23: An immunogenic composition comprising a polypeptide comprising (i) an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 186 and/or (ii) a fragment of SEQ ID NO: 186 , wherein the fragment of SEQ ID NO: 186 comprises 16 or more consecutive amino acids of the amino acid sequence of SEQ ID NO: 186.24: The composition of claim 23 , wherein the fragment comprises 16 consecutive amino acids of the amino acid sequence of SEQ ID NO: 186.25: The composition of claim 24 , wherein the fragment comprises 20 consecutive amino acids of the amino acid sequence of SEQ ID NO: 186.26: The composition of claim 23 , wherein the fragment lacks the first 20 N-terminal amino acids of SEQ ID NO: 186.27S. aureus: The composition of claim 23 , wherein the composition further comprises one or more of the following polypeptides: an esxA antigen; an esxB antigen; an hla antigen; an sta006 antigen; an sta011 antigen; a LukE antigen; and a spa antigen.28: The composition of claim 23 , further comprising an adjuvant.29S. aureus: The composition of claim 23 , further comprising: one or more conjugates of (i) a exopolysaccharide and (ii) a carrier protein.30S. aureus: The composition of claim 23 , further comprising: one or more conjugates of (i) a capsular polysaccharide and (ii) a carrier protein.31: A method for raising an immune response in a mammal comprising the step of administering to the mammal an effective amount of the composition of .32: A polypeptide of formula NH-A-(-X-L-)-B—COOH claim 23 , wherein:X is an amino acid sequence of a staphylococcal antigen sta116;L is an optional linker amino acid sequence;A is an optional N-terminal amino acid sequence;B is an optional C-terminal amino acid sequence; andn is an integer of 2 or more. ...

CONJUGATION OF STAPHYLOCOCCUS AUREUS TYPE 5 AND TYPE 8 CAPSULAR POLYSACCHARIDES

The invention provides a process for preparing a conjugate of a type 5 or type 8 capsular polysaccharide and a carrier molecule, comprising the steps of: (a) depolymerising the capsular polysaccharide, to give a polysaccharide fragment; (b) oxidising the fragment in order to introduce an aldehyde group into at least one saccharide residue in the fragment, to give an oxidised saccharide residue; and (c) coupling the oxidised saccharide residue to a carrier molecule via the aldehyde group, thereby giving the conjugate. The coupling in step (c) may be direct, or may be via a linker molecule. The invention also provides a conjugate obtained or obtainable by this process. 1S.aureus. A process for preparing a conjugate of a type 5 or type 8 capsular polysaccharide and a carrier molecule , comprising the steps of: (a) depolymerising the capsular polysaccharide , to give a polysaccharide fragment; (b) oxidising the fragment in order to introduce an aldehyde group into at least one saccharide residue in the fragment , to give an oxidised saccharide residue; and (c) coupling the oxidised saccharide residue to a carrier molecule via the aldehyde group , thereby giving the conjugate.2. A process for treating a S.aureus type 5 capsular polysaccharide comprising the step of depolymerising the capsular polysaccharide , to give a polysaccharide fragment having a β-D-FucNAc-(1→moiety at its non-reducing terminus.3S.aureus. A process for treating a type 8 capsular polysaccharide comprising the step of depolymerising the capsular polysaccharide , to give a polysaccharide fragment having an α-D-FucNAc-(1→moiety at is non-reducing terminus.4. The process according to any preceding claim , wherein the depolymerising is carried out by acid hydrolysis using acetic acid.5. The process according to any preceding claim , wherein the average molecular mass of the fragment is between 5 and 100 kDa.6. The process according to any preceding claim , wherein the degree of O-acetylation of the ...

ADJUVANTING MENINGOCOCCAL FACTOR H BINDING PROTEIN

Factor H binding protein (fHBP) has been proposed for use in immunising against serogroup B meningococcus (‘MenB’). This antigen can be efficiently adsorbed to an aluminium hydroxyphosphate adjuvant by (i) ensuring that adsorption takes place at a pH which is equal to or below the adjuvant's point of zero charge (PZC), and/or (ii) selecting a fHBP and adjuvant with an isoelectric point/PZC within the range of 5.0 to 7, and/or (iii) selecting a fHBP with an isoelectric point above the adjuvant's PZC and using a buffer to bring the pH to within 1.2 pH units of the PZC. The adsorption is particularly useful for compositions which include multiple fHBP variants, and also in situations where an aluminium hydroxide adjuvant should be avoided. Buffered pharmaceutical compositions can include at least two different meningococcal fHBP antigens, both of which are at least 85% adsorbed to aluminium hydroxyphosphate adjuvant. 1. A buffered immunogenic composition comprising at least two different meningococcal fHBP antigens , both of which are at least 85% adsorbed to aluminium hydroxyphosphate adjuvant.2. The composition of claim 1 , wherein (i) each of the two different fHBP antigens has an isoelectric point between 5.0 and 7.0 claim 1 , and (ii) the aluminium hydroxyphosphate adjuvant has a point of zero charge between 5.0 and 7.0.3. The composition of claim 2 , wherein the pH of the buffered composition is in the range of 5.0 to 7.0.4. An immunogenic composition comprising two different meningococcal fHBP antigens claim 2 , both of which are adsorbed to aluminium hydroxyphosphate adjuvant claim 2 , wherein (i) both of the meningococcal fHBP antigens have an isoelectric point between 5.0 and 7.0 claim 2 , and (ii) the aluminium hydroxyphosphate adjuvant has a point of zero charge between 5.0 and 7.0.5. A buffered immunogenic composition comprising two different meningococcal fHBP antigens claim 2 , both adsorbed to aluminium hydroxyphosphate adjuvant claim 2 , wherein (i) ...

METHODS FOR PROTEIN PURIFICATION

The present invention relates to methods of protein purification, in particular using ion exchange chromatography. Modified proteins and peptide tags suitable for use in purification by ion exchange chromatography are provided, as are related methods. 1. A fusion protein suitable for purification via ion exchange chromatography , which protein comprises(i) a protein of interest(ii) a peptide tag at the N or C terminus;{'sub': n', 'n', 'n', 'n, 'wherein the peptide tag comprises (HR), (PR), (SR)or (PSR), where ‘n’ is an integer from 2 to 6 inclusive.'}2. A fusion protein comprising a protein of interest covalently linked directly or indirectly to a peptide tag which is capable of binding to an ion exchange resin , wherein the peptide tag comprises (HR) , (PR) , (SR)or (PSR) , where ‘n’ is an integer from 2 to 6 inclusive.3. A fusion protein according to or , wherein the peptide tag is from 4 to 20 amino acids in length.4. A fusion protein according to claim 3 , wherein the peptide tag is from 4 to 12 amino acids in length.5. A fusion protein according to any one of to claim 3 , wherein the peptide tag comprises an amino acid sequence of any one of SEQ ID Nos 4-6 claim 3 , 8 and 9.6. A fusion protein according to claim 5 , wherein the peptide tag consists of an amino acid sequence of any one of SEQ ID Nos 4-6 claim 5 , 8 and 9.7. A fusion protein according to any one of to claim 5 , further comprising a linker between the protein of interest and the peptide tag.8. A fusion protein according to claim 7 , wherein the linker comprises GG claim 7 , GS claim 7 , SS claim 7 , SG claim 7 , or GGSGG.9. A fusion protein according to any one of to claim 7 , wherein the protein of interest is an antigenic protein or a carrier protein.10C. jejuniHaemophilus influenzaePseudomonas aeruginosaStreptococcus. pneumoniaeS. aureusS. aureus.. A fusion protein according to claim 9 , wherein the protein of interest is tetanus toxoid (TT) claim 9 , diphtheria toxoid (DT) claim 9 , CRM claim ...

VACCINATION

Immunogenic compositions for use in and methods for protecting against Herpes Zoster (shingles). 126.-. (canceled)27. A method for prevention of herpes zoster (HZ) in a human subject comprising the step of administering to said human subject one dose of an immunogenic composition comprising a Varicella Zoster Virus (VZV) gE antigen truncated to remove the carboxy terminal anchor region , in combination with an adjuvant comprising a saponin , a TLR-4 agonist and liposomes.2837-. (canceled)38. The method according to claim 27 , wherein the human subject is 50 years of age or older.39. The method according to claim 27 , wherein the human subject is 70 years of age or older.40. The method according to claim 27 , wherein the human subject received a live-attenuated VZV vaccine at least 3 years earlier.41. The method according to claim 27 , wherein the VZV gE antigen is not in the form of a fusion protein.42. The method according to claim 27 , wherein the VZV gE antigen comprises the sequence of SEQ ID NO: 1.43. The method according to claim 27 , wherein the VZV gE antigen is present in an amount of between 20 to 100 μg per dose.44. The method according to claim 27 , wherein the VZV antigen is present in an amount of 50 μg per dose.45. The method according to claim 27 , wherein the saponin is QS21.46. The method according to claim 45 , wherein the QS21 is present in an amount of 1 to 100 μg per dose.47. The method according to claim 45 , wherein the QS21 is present in an amount of 50 μg per dose.48. The method according to claim 27 , wherein the TLR-4 agonist is 3-O-desacyl-4′-Monophosphoryl Lipid A (3D-MPL).49. The method according to claim 48 , wherein the 3D-MPL is present in an amount of at least 25 μg per dose.50. The method according to claim 27 , wherein the liposomes further comprise a sterol.51. The method according to claim 27 , wherein the liposomes comprise dioleoyl phosphatidylcholine (DOPC) and cholesterol.52. The method according to claim 27 , wherein the ...

STAPHYLOCOCCUS AUREUS PROTEINS AND NUCLEIC ACIDS

The invention provides proteins from including amino acid sequences and the corresponding nucleotide sequences. The proteins are useful for vaccines, immunogenic compositions, diagnostics, enzymatic studies and also as targets for antibiotics. 1. (canceled)2. A composition comprising: an isolated polypeptide comprising an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 3178.3. The composition of claim 2 , wherein the amino acid sequence is at least 99% identical to SEQ ID NO: 3178.4. A composition comprising a hybrid polypeptide represented by the formula NH2—A—[—X—L—]n-B—COOH claim 2 , wherein X is an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 3178; L is an optional linker amino acid sequence; A is an optional N-terminal amino acid sequence; B is an optional C-terminal amino acid sequence; and n is an integer greater than 1 claim 2 , wherein X may be the same sequence or have different amino acid sequences.5. The composition of or claim 2 , further comprising a pharmaceutically acceptable carrier.6Helicobacter pyloriN. meningitidisN. meningitidisN. meningitidisStreptococcus pneumoniaeBordetella pertussisHaemophilus influenzaeN. gonorrhoeaeChlamydia pneumoniaeStreptococcus agalactiaeStreptococcus pyogenesChlamydia trachomatisPorphyromonas gingivalisMoraxella catarrhalis.. The composition of or claim 2 , further comprising one or more antigens selected from the group consisting of a protein antigen from ; a protein antigen from serogroup B; an outer-membrane vesicle (OMV) preparation from ; a saccharide antigen from serogroup A claim 2 , C claim 2 , W135 and/or Y; a saccharide antigen from ; an antigen from hepatitis A virus; an antigen from hepatitis B virus; an antigen from hepatitis C virus; an antigen from ; a diphtheria antigen; a tetanus antigen; a saccharide antigen from B; an antigen from ; an antigen from ; an antigen from ; an antigen from ; an antigen from ; an antigen from ; polio antigen(s); rabies ...