title: Characterization and identification of vaccine candidate proteins through analysis of the group A Streptococcus surface proteome.
abstract: We describe a proteomic approach for identifying bacterial surface-exposed proteins quickly and reliably for their use as vaccine candidates. Whole cells are treated with proteases to selectively digest protruding proteins that are subsequently identified by mass spectrometry analysis of the released peptides. When applied to the sequenced M1_SF370 group A Streptococcus strain, 68 PSORT-predicted surface-associated proteins were identified, including most of the protective antigens described in the literature. The number of surface-exposed proteins varied from strain to strain, most likely as a consequence of different capsule content. The surface-exposed proteins of the highly virulent M23_DSM2071 strain included 17 proteins, 15 in common with M1_SF370. When 14 of the 17 proteins were expressed in E. coli and tested in the mouse for their capacity to confer protection against a lethal dose of M23_DSM2071, one new protective antigen (Spy0416) was identified. This strategy overcomes the difficulties so far encountered in surface protein characterization and has great potential in vaccine discovery.
authors.affiliation: Chiron Vaccines, Via Fiorentina, 1 53100 Siena, Italy.
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: Rodríguez-Ortega
authors.forename: Nathalie
authors.initials: N
authors.lastname: Norais
authors.forename: Giuliano
authors.initials: G
authors.lastname: Bensi
authors.forename: Sabrina
authors.initials: S
authors.lastname: Liberatori
authors.forename: Sabrina
authors.initials: S
authors.lastname: Capo
authors.forename: Marirosa
authors.initials: M
authors.lastname: Mora
authors.forename: Maria
authors.initials: M
authors.lastname: Scarselli
authors.forename: Francesco
authors.initials: F
authors.lastname: Doro
authors.forename: Germano
authors.initials: G
authors.lastname: Ferrari
authors.forename: Ignazio
authors.initials: I
authors.lastname: Garaguso
authors.forename: Tiziana
authors.initials: T
authors.lastname: Maggi
authors.forename: Anita
authors.initials: A
authors.lastname: Neumann
authors.forename: Alessia
authors.initials: A
authors.lastname: Covre
authors.forename: John L
authors.initials: JL
authors.lastname: Telford
authors.forename: Guido
authors.initials: G
authors.lastname: Grandi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000032:analysis / Q000737:chemistry / Q000276:immunology; D001428:Bacterial Vaccines / Q000032:analysis* / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods; D015195:Drug Design; D013058:Mass Spectrometry / Q000379:methods; D008565:Membrane Proteins / Q000032:analysis* / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D010449:Peptide Mapping / Q000379:methods; D020543:Proteome / Q000032:analysis* / Q000737:chemistry / Q000276:immunology; D013290:Streptococcal Infections / Q000276:immunology* / Q000517:prevention & control; D013297:Streptococcus pyogenes / Q000276:immunology / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D008565:Membrane Proteins; D020543:Proteome