title: Prevention of pneumococcal disease in mice immunized with conserved surface-accessible proteins.
abstract: The development of a vaccine against Streptococcus pneumoniae has been complicated by the existence of at least 90 antigenically distinct capsular serotypes. Common protein-based vaccines could represent the best strategy to prevent pneumococcal infections, regardless of serotype. In the present study, the immunoscreening of an S. pneumoniae genomic library allowed the identification of a novel immune protein target, BVH-3. We demonstrate that immunization of mice with BVH-3 elicits protective immunity against experimental sepsis and pneumonia. Sequence analysis revealed that the bvh-3 gene is highly conserved within the species. Since the BVH-3 protein shows homology at its amino-terminal end with other pneumococcal proteins, it was of interest to determine if protection was due to the homologous or to the protein-specific regions. Immunoprotection studies using recombinant BVH-3 and BVH-3-related protein fragments as antigens allowed the localization of surface-exposed and protective epitopes at the protein-specific carboxyl termini, thus establishing that BVH-3 is distinct from other previously reported protective protein antigens. Immunization with a chimeric protein comprising the carboxyl-terminal regions of BVH-3 and of a BVH-3-related protein improved the protection by targeting two surface pneumococcal components. Thus, BVH-3 and the chimeric protein hold strong promise as vaccine components to control pneumococcal disease.
authors.affiliation: Unité de Recherche en Vaccinologie, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Sainte-Foy, Québec G1V 4G2, Canada. Josee.Hamel@crchul.ulaval.ca
authors.forename: Josée
authors.initials: J
authors.lastname: Hamel
authors.forename: Nathalie
authors.initials: N
authors.lastname: Charland
authors.forename: Isabelle
authors.initials: I
authors.lastname: Pineau
authors.forename: Catherine
authors.initials: C
authors.lastname: Ouellet
authors.forename: Stéphane
authors.initials: S
authors.lastname: Rioux
authors.forename: Denis
authors.initials: D
authors.lastname: Martin
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Brodeur
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D017124:Conserved Sequence; D000939:Epitopes / Q000235:genetics; D005798:Genes, Bacterial; D006801:Humans; D007114:Immunization; D007116:Immunization, Passive; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011008:Pneumococcal Infections / Q000276:immunology* / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D011018:Pneumonia, Pneumococcal / Q000276:immunology / Q000517:prevention & control; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D018805:Sepsis / Q000276:immunology / Q000517:prevention & control; D017386:Sequence Homology, Amino Acid; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification / Q000235:genetics / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D000939:Epitopes; D022242:Pneumococcal Vaccines; D011994:Recombinant Proteins