title: Formulation, stability and immunogenicity of a trivalent pneumococcal protein vaccine formulated with aluminum salt adjuvants.
abstract: We investigated the immunogenicity, stability and adsorption properties of an experimental pneumococcal vaccine composed of three protein vaccine antigens; Pneumococcal histidine triad protein D, (PhtD), Pneumococcal choline-binding protein A (PcpA) and genetically detoxified pneumolysin D1 (PlyD1) formulated with aluminum salt adjuvants. Immunogenicity studies conducted in BALB/c mice showed that antibody responses to each antigen adjuvanted with aluminum hydroxide (AH) were significantly higher than when adjuvanted with aluminum phosphate (AP) or formulated without adjuvant. Lower microenvironment pH and decreased strength of antigen adsorption significantly improved the stability of antigens. The stability of PcpA and PlyD1 assessed by RP-HPLC correlated well with the immunogenicity of these antigens in mice and showed that pretreatment of the aluminum hydroxide adjuvant with phosphate ions improved their stability. Adjuvant dose-ranging studies showed that 28 μg Al/dose to be the concentration of adjuvant resulting in optimal immunogenicity of the trivalent vaccine formulation. Taken together, the results of theses studies suggest that the type of aluminum salt, strength of adsorption and microenvironment pH have a significant impact on the immunogenicity and chemical stability of an experimental vaccine composed of the three pneumococcal protein antigens, PhtD, PcpA, and PlyD1.
authors.affiliation: Product Concept and Development, Sanofi Pasteur, Toronto, ON, M2R 3T4, Canada.
authors.forename: Belma
authors.initials: B
authors.lastname: Ljutic
authors.forename: Martina
authors.initials: M
authors.lastname: Ochs
authors.forename: Benjamin
authors.initials: B
authors.lastname: Messham
authors.forename: Marin
authors.initials: M
authors.lastname: Ming
authors.forename: Annie
authors.initials: A
authors.lastname: Dookie
authors.forename: Kevin
authors.initials: K
authors.lastname: Harper
authors.forename: Salvador F
authors.initials: SF
authors.lastname: Ausar
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D017607:Aluminum Compounds / Q000008:administration & dosage; D000536:Aluminum Hydroxide / Q000008:administration & dosage*; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D004355:Drug Stability; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010710:Phosphates / Q000008:administration & dosage; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D010710:Phosphates; D022242:Pneumococcal Vaccines; D022223:Vaccines, Subunit; D000536:Aluminum Hydroxide; C012714:aluminum phosphate