title: Multi high-throughput approach for highly selective identification of vaccine candidates: the Group A Streptococcus case.
abstract: We propose an experimental strategy for highly accurate selection of candidates for bacterial vaccines without using in vitro and/or in vivo protection assays. Starting from the observation that efficacious vaccines are constituted by conserved, surface-associated and/or secreted components, the strategy contemplates the parallel application of three high throughput technologies, i.e. mass spectrometry-based proteomics, protein array, and flow-cytometry analysis, to identify this category of proteins, and is based on the assumption that the antigens identified by all three technologies are the protective ones. When we tested this strategy for Group A Streptococcus, we selected a total of 40 proteins, of which only six identified by all three approaches. When the 40 proteins were tested in a mouse model, only six were found to be protective and five of these belonged to the group of antigens in common to the three technologies. Finally, a combination of three protective antigens conferred broad protection against a panel of four different Group A Streptococcus strains. This approach may find general application as an accelerated and highly accurate path to bacterial vaccine discovery.
authors.affiliation: Novartis Vaccines and Diagnostics, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Bensi
authors.forename: Marirosa
authors.initials: M
authors.lastname: Mora
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tuscano
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Biagini
authors.forename: Emiliano
authors.initials: E
authors.lastname: Chiarot
authors.forename: Mauro
authors.initials: M
authors.lastname: Bombaci
authors.forename: Sabrina
authors.initials: S
authors.lastname: Capo
authors.forename: Fabiana
authors.initials: F
authors.lastname: Falugi
authors.forename: Andrea G O
authors.initials: AG
authors.lastname: Manetti
authors.forename: Paolo
authors.initials: P
authors.lastname: Donato
authors.forename: Erwin
authors.initials: E
authors.lastname: Swennen
authors.forename: Marilena
authors.initials: M
authors.lastname: Gallotta
authors.forename: Manuela
authors.initials: M
authors.lastname: Garibaldi
authors.forename: Vittoria
authors.initials: V
authors.lastname: Pinto
authors.forename: Nico
authors.initials: N
authors.lastname: Chiappini
authors.forename: James M
authors.initials: JM
authors.lastname: Musser
authors.forename: Robert
authors.initials: R
authors.lastname: Janulczyk
authors.forename: Massimo
authors.initials: M
authors.lastname: Mariani
authors.forename: Maria
authors.initials: M
authors.lastname: Scarselli
authors.forename: John L
authors.initials: JL
authors.lastname: Telford
authors.forename: Renata
authors.initials: R
authors.lastname: Grifantini
authors.forename: Nathalie
authors.initials: N
authors.lastname: Norais
authors.forename: Immaculada
authors.initials: I
authors.lastname: Margarit
authors.forename: Guido
authors.initials: G
authors.lastname: Grandi
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001428:Bacterial Vaccines / Q000008:administration & dosage*; D016000:Cluster Analysis; D005260:Female; D005434:Flow Cytometry; D006461:Hemolysis; D006801:Humans; D051379:Mice; D010612:Pharyngitis / Q000097:blood / Q000276:immunology / Q000382:microbiology; D040081:Protein Array Analysis; D020543:Proteome / Q000276:immunology / Q000378:metabolism; D012756:Sheep; D013290:Streptococcal Infections / Q000097:blood / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D013297:Streptococcus pyogenes / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D020543:Proteome