Glaxosmithkline Biologicals Sa

Novartis Ag

Seqirus UK Limited

Novartis Vaccines and Diagnostics Srl

Novartis Caccines and Diagnostics Srl

Glaxosmithkline Vaccines S.r.l.

Massimo Maffei

Mario Contorni

Derek T O'Hagan

Mariagrazia Pizza

Guido Grandi

Manmohan Singh

Paolo Costantino

Lorenzo Tarli

Nicola Groth

Francesco Berti

Marzia Monica Giuliani

John Telford

Immaculada Margarit Y Ros

Domenico Maione

Jina Kazzaz

Oretta Finco

Mildred Ugozzoli

Donatella Mannucci

Anja Seubert

Marzia Giuliani

The invention provides an immunogenic composition comprising OMVs and (a) acellular pertussis antigen, (b) a tetanus toxoid and (c) a diphtheria toxoid, wherein the OMVs are derived from. The invention also provides compositions for use in a method for raising an immune response in a patient, comprising the step of administering to the patient a composition of the invention.

Immunogenic compositions comprising OMVs, an acellular pertussis antigen, a tetanus toxoid and a diphtheria toxoid

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 &#x3e;12 &#x3bc;g/ml per strain. In some embodiments the squalene concentration is &#x3c;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.

Influenza vaccines with reduced amounts of squalene

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.

Adjuvanting meningococcal factor H binding protein

Factor H binding protein (fHBP) has been proposed for use in immunizing against serogroup B meningococcus ('MenB'). This antigen can be efficiently adsorbed to an aluminum 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 aluminum 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 aluminum hydroxyphosphate adjuvant.

The invention uses polypeptide antigens and/or OMVs to immunize against serogroups A, C, W135 and Y (and against serogroup Y in particular). Serogroup B polypeptides can achieve this protection, thus permitting a single polypeptide-based vaccine to be used for protecting against all of serogroups A, B, C, W135 and Y.

Immunising against meningococcal serogroup Y using proteins

The invention provides an immunogenic composition comprising one or more GBS conjugates and one or more antigens selected from: a) cellular or acellular pertussis antigen, b) a tetanus toxoid, c) a diphtheria toxoid and d) an inactivated polio virus antigen, wherein each GBS conjugate is a group Bcapsular saccharide conjugated to a carrier protein. The invention also provides a method for raising an immune response in a patient, comprising the step of administering to the patient a composition of the invention.

Immunogenic compositions

A liquid D-T-Pa component is used to reconstitute a lyophilised meningococcal component, thereby producing a combined vaccine.

Mixing lyophilised meningococcal vaccines with D-T-Pa vaccines

Provided herein are combination vaccines comprising antigens for protecting a subject against at least diphtheria, tetanus, pertussis and Hib, wherein: (a) the antigen for protecting against Hib is a conjugate of a Hib capsular saccharide; (b) the concentration of the Hib conjugate in the vaccine is &#x3c;15 &#x3bc;g/ml; and (c) the Hib conjugate has never been lyophilized.

Combination vaccines with low dose of Hib conjugate

Conjugated capsular saccharides from meningococcal serogroups C, W135 and Y are safe and immunogenic in humans when combined in a single dose. This effect is retained when a conjugated capsular saccharide from serogroup A is added. These conjugated antigens can be stably combined in a single aqueous dose without the need for lyophilization. Broad protection against serogroup B infection can be achieved by using a small number of defined polypeptide antigens. These polypeptide antigens can be combined with the saccharide antigens without loss of protective efficacy for any of the five serogroups. Efficacy if retained even if a Hib conjugate is added. The efficacy of a serogroup W135 conjugate is enhanced by addition of protein antigens derived from a serogroup B strain. Addition of a Hib conjugate to meningococcal conjugates enhances the overall activity against meningococcus serogroup W135.

Liquid vaccines for multiple meningococcal serogroups

To improve the stability of vaccines comprising aluminum salt(s), the invention uses the amino acid histidine. This can improve pH stability and adjuvant adsorption and can reduce antigen hydrolysis. Histidine is preferably present during adsorption to the aluminum salt(s). The antigen in the vaccine may be a protein or a saccharide and is preferably from N. meningitidis.

Vaccines comprising aluminum adjuvants and histidine

Vaccines have been studied that comprise (a) D-T-Pw-HepB-Hib antigens and (b) one or more meningococcal conjugate antigens. A number of improvements and variations of these vaccines have been discovered. The vaccines can be prepared extemporaneously at the time of use by mixing together two components: (a) a first component comprising D, T, wP and HBsAg antigens; and (b) a second component comprising a Hib conjugate and one or more meningococcal conjugates.

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Siena, Italy

Mario Contorni