title: Development of a multicomponent vaccine for Streptococcus pyogenes based on the antigenic targets of IVIG.
abstract: OBJECTIVE
  Despite over a century of research and the careful scrutiny of many promising targets, there is currently no vaccine available for the prevention of Streptococcus pyogenes infection. Through analysis of the protective, anti-streptococcal components of pooled human immunoglobulin, we previously identified ten highly conserved and invariant S. pyogenes antigens that contribute to anti-streptococcal immunity in the adult population. We sought to emulate population immunity to S. pyogenes through a process of active vaccination, using the antigens targeted by pooled human immunoglobulin.
  
  
  METHODS
  Seven targets were produced recombinantly and mixed to form a multicomponent vaccine (Spy7). Vaccinated mice were challenged with S. pyogenes isolates representing four globally relevant serotypes (M1, M3, M12 and M89) using an established model of invasive disease.
  
  
  RESULTS
  Vaccination with Spy7 stimulated the production of anti-streptococcal antibodies, and limited systemic dissemination of M1 and M3 S. pyogenes from an intramuscular infection focus. Vaccination additionally attenuated disease severity due to M1 S. pyogenes as evidenced by reduction in weight loss, and modulated cytokine release.
  
  
  CONCLUSIONS
  Spy7 vaccination successfully stimulated the generation of protective anti-streptococcal immunity in vivo. Identification of reactive antigens using pooled human immunoglobulin may represent a novel route to vaccine discovery for extracellular bacteria.
authors.affiliation: Faculty of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Reglinski
authors.affiliation: Faculty of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, United Kingdom.
authors.forename: Nicola N
authors.initials: NN
authors.lastname: Lynskey
authors.affiliation: Faculty of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, United Kingdom.
authors.forename: Yoon Jung
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Faculty of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, United Kingdom.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Edwards
authors.affiliation: Faculty of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, United Kingdom. Electronic address: s.sriskandan@imperial.ac.uk.
authors.forename: Shiranee
authors.initials: S
authors.lastname: Sriskandan
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D016756:Immunoglobulins, Intravenous / Q000276:immunology*; D051379:Mice; D013290:Streptococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D022541:Streptococcal Vaccines / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D016207:Cytokines; D016756:Immunoglobulins, Intravenous; D022541:Streptococcal Vaccines
keywords: Group A Streptococcus; IVIG; Population immunity; Streptococcus pyogenes; Vaccine