Abstract: Particle compositions comprising adsorbed RNA replicons as well as methods of making and using the same are described.

Abstract: Influenza vaccines include hemagglutinin from at least one influenza A virus strain and at least one influenza B virus strain. They also include an oil-in-water emulsion adjuvant with submicron oil droplets, comprising squalene. In some embodiments the hemagglutinin concentration is >12 ?g/ml per strain. In some embodiments the squalene concentration is <19 mg/ml. In some embodiments the vaccine is mercury-free. In some embodiments the vaccine has a unit dose volume between 0.2-0.3 mL. In some embodiments the squalene concentration is 9.75 mg/mL or 4.88 mg/mL. In some embodiments the vaccine includes antigens from two influenza A virus strains and two influenza B virus strains.

Abstract: An intradermal delivery system comprises an immunogenic composition comprising a TLR agonist and immunogen and a microneedle. The immunogenic composition may comprise a solid biodegradable microneedle or a solid coated microneedle. The intradermal delivery system may be formulated into a skin patch.

Abstract: Particle compositions comprising adsorbed RNA replicons as well as methods of making and using the same are described.

Abstract: Influenza viruses have traditionally been administered by intramuscular injection. The invention is based on the idea of using alternative routes of delivery for influenza vaccines, more specifically routes that do not require as large a dose of antigen. Delivery of influenza antigen to the Langerhans cells is the route of choice according to the invention. This route has been found to be particularly useful for vaccinating patients who are naïve to influenza virus (i.e. have not previously mounted an immune response to an influenza virus), which means that it is advantageous for immunising young children.

Abstract: While oil-in-water emulsions are excellent adjuvants for influenza vaccines, their efficacy can be improved by additionally including other immunostimulating agent(s) to improve cytokine responses, such as y-interferon response. Thus, a vaccine comprises (i) an influenza virus antigen; (ii) an oil-in-water emulsion adjuvant; and (iii) a cytokine-inducing agent.

Abstract: Immunogenic compositions comprising microparticles with adsorbed toxoid antigen and/or polysaccharide-containing antigen are disclosed. The immunogenic microparticle compositions comprise (a) polymer microparticles comprising a biodegradable polymer; (b) an antigen adsorbed to the microparticles selected from (i) a toxoid antigen, such as a tetanus toxoid, a diphtheria toxoid, or a combination thereof, and/or (ii) a polysaccharide containing antigen, such as a Hib polysaccharide antigen, a Hib conjugate antigen comprising polysaccharide and polypeptide regions, a meningococcal polysaccharide antigen, a meningococcal conjugate antigen comprising polysaccharide and polypeptide regions, a pneumococcal polysaccharide antigen, and a pneumococcal conjugate antigen comprising polysaccharide and polypeptide regions or a combination thereof; and (c) a pharmaceutically acceptable excipient.

Abstract: 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.

Abstract: The efficacy of S. pneumoniae vaccines can be enhanced by adjuvanting S. pneumoniae saccharide and/or protein antigens with a mixture of a TLR agonist (preferably a TLR7 agonist) and an insoluble metal salt (preferably an aluminium salt). The TLR agonist is typically adsorbed to the metal salt. The S. pneumoniae antigen can also be adsorbed to the metal salt.

Abstract: An immunogenic composition comprising a diphtheria toxoid, a tetanus toxoid, a pertussis toxoid, an aluminium salt adjuvant, and a TLR4 agonist. Preferably, the TLR4 agonist and/or at least one of the toxoids is/are adsorbed to the aluminium salt adjuvant.

Abstract: Microparticles with adsorbed polynucleotide-containing species, compositions containing the same, methods of making such microparticles, and uses thereof are disclosed. The microparticles comprise (a) a biodegradable polymer, such as a polyhydroxy butyric acid, a polycaprolactone, a polyorthoester, a polyanhydride, or a polycyanoacrylate, (b) a cationic surfactant such as cetyltrimethylammonium bromide, (c) and a polynucleotide-containing species adsorbed on the surface of the microparticles, wherein the polynucleotide-containing species constitutes at least 5 percent of the total weight of said microparticles. Examples of polynucleotide-containing species include polynucleotide-containing immunological adjuvants, such as CpG oligonucleotides, and polynucleotide-containing species that encode polypeptide-containing antigens, such as RNA and DNA vector constructs.

Abstract: The efficacy of rabies vaccines can be enhanced by adjuvanting rabies virus immunogens with a mixture of a TLR agonist (preferably a TLR7 agonist) and an insoluble metal salt (preferably an aluminium salt). The TLR agonist is typically adsorbed to the metal salt. The rabies virus immunogen can also be adsorbed to the metal salt.

Abstract: Immunogenic compositions are disclosed which comprise microparticles that comprise a biodegradable polymer, an immunological adjuvant and a tocol-family compound. Methods of making and using such microparticle compositions are also disclosed.

Abstract: An immunological adjuvant comprises an aluminum salt, an immunostimulatory oligonucleotide and a polycationic polymer, wherein the oligonucleotide and the polymer ideally associate with each other to form a complex. The adjuvant can be included in a composition with an immunogen e.g. to elicit an immune response that protects against a bacterial disease or a fungal disease.

Abstract: Improved methods for the production of reassortant influenza viruses are provided.

Abstract: Influenza vaccines containing insoluble particulate adjuvants have been found to elicit an IgG response that is primarily a TH2 response (IgG1). This response can be shifted towards a TH1 response (IgG2a) by including immunopotentiators in the compositions. Thus the invention provides an immunogenic composition comprising: (i) an influenza virus antigen; (ii) an insoluble particulate adjuvant; and (iii) a immunopotentiator.

Abstract: The invention provides, inter alia, immunogenic compositions that comprise (a) a first antigen, (b) at least first and second adjuvants, wherein the first adjuvant comprises microparticles and wherein the second adjuvant comprises an imidazoquinoline compound, and (c) a pharmaceutically acceptable excipient, which compositions elicits an immune response when administered to a vertebrate subject. The invention also provides methods of producing immunogenic compositions and methods for using immunogenic compositions (e.g., for treatment), among other benefits.

Abstract: 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.

Abstract: This invention generally relates to cationic oil-in-water emulsions that can be used to deliver nucleic acid molecules, such as an RNA molecule. The emulsion particles comprise an oil core and a cationic lipid. The emulsion particles have an average diameter of about 80 nm to about 180 nm, and the emulsion have an N/P ratio of at least 1.1:1.

Abstract: A combination of CpG oligonucleotides and polymer microparticles is an extremely effective adjuvant for Neisserial antigens. The invention therefore provides a composition comprising: (a) a Neisserial antigen; (b) a CpG oligonucleotide; and (c) a biodegradable polymer microparticle.