title: Identifying protective Streptococcus pyogenes vaccine antigens recognized by both B and T cells in human adults and children.
abstract: No commercial vaccine exists against Group A streptococci (GAS; Streptococcus pyogenes) and only little is known about anti-GAS protective immunity. In our effort to discover new protective vaccine candidates, we selected 21 antigens based on an in silico evaluation. These were all well-conserved among different GAS strains, upregulated in host-pathogen interaction studies, and predicted to be extracellular or associated with the surface of the bacteria. The antigens were tested for both antibody recognition and T cell responses in human adults and children. The antigenicity of a selected group of antigens was further validated using a high-density peptide array technology that also identified the linear epitopes. Based on immunological recognition, four targets were selected and tested for protective capabilities in an experimental GAS infection model in mice. Shown for the first time, three of these targets (spy0469, spy1228 and spy1801) conferred significant protection whereas one (spy1643) did not.
authors.affiliation: Statens Serum Institut, Department of Infectious Disease Immunology, Denmark.|Department of Immunology and Microbiology, University of Copenhagen, Denmark.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Mortensen
authors.affiliation: Department of Pediatrics, Copenhagen University Hospital, Hvidovre, Denmark.
authors.forename: Thomas Nørrelykke
authors.initials: TN
authors.lastname: Nissen
authors.affiliation: Statens Serum Institut, Department of Infectious Disease Immunology, Denmark.
authors.forename: Sine
authors.initials: S
authors.lastname: Fredslund
authors.affiliation: Statens Serum Institut, Department of Infectious Disease Immunology, Denmark.
authors.forename: Ida
authors.initials: I
authors.lastname: Rosenkrands
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Denmark.
authors.forename: Jan Pravsgaard
authors.initials: JP
authors.lastname: Christensen
authors.affiliation: Statens Serum Institut, Department of Infectious Disease Immunology, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.affiliation: Statens Serum Institut, Department of Infectious Disease Immunology, Denmark.
authors.forename: Jes
authors.initials: J
authors.lastname: Dietrich
mesh_terms: D000328:Adult; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002648:Child; D003429:Cross Reactions / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D009206:Myocardium / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D015203:Reproducibility of Results; D013290:Streptococcal Infections / Q000276:immunology / Q000517:prevention & control; D022541:Streptococcal Vaccines / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D000939:Epitopes; D007074:Immunoglobulin G; D022541:Streptococcal Vaccines