Identifying protective Streptococcus pyogenes vaccine antigens recognized by both B and T cells in human adults and children

Scientific Reports
Rasmus MortensenJes Dietrich

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.

References

Jun 1, 1988·The Journal of Experimental Medicine·D Bessen, V A Fischetti
May 4, 1999·The Journal of Clinical Investigation·J B DaleD L Hasty
Jul 25, 2000·Clinical Microbiology Reviews·M W Cunningham
Oct 9, 2002·Molecular Microbiology·Carine MercierSaulius Kulakauskas
Feb 8, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jovanka M VoyichFrank R DeLeo
Jun 16, 2005·Proceedings of the National Academy of Sciences of the United States of America·Kimmo VirtanevaJames M Musser
Oct 29, 2005·The Lancet Infectious Diseases·Jonathan R CarapetisMartin Weber
Apr 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kellen C FaéLuiza Guilherme
Aug 29, 2006·The American Journal of Pathology·Morag R GrahamJames M Musser
Jan 26, 2007·Journal of Virology·Thomas C FriedrichDavid I Watkins
Apr 24, 2008·Molecular Microbiology·Girbe BuistOscar P Kuipers
Oct 15, 2008·Vaccine·Gregory J TobinPeter L Nara
Jul 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Claus Sindbjerg AagaardPeter Andersen
Oct 3, 2009·Current Opinion in Infectious Diseases·Andrew C SteerJonathan R Carapetis
Mar 17, 2010·Proceedings of the National Academy of Sciences of the United States of America·Beinan WangP Patrick Cleary
Apr 25, 2012·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Anna HenninghamMark J Walker
Dec 20, 2012·Human Vaccines & Immunotherapeutics·Ivette Caro-AguilarJulie M Skinner
Jan 19, 2013·The Pediatric Infectious Disease Journal·Andrew C SteerJonathan R Carapetis
Nov 6, 2013·Immunology and Cell Biology·Louis M Tsai, Di Yu
May 7, 2014·The Journal of Infectious Diseases·Martina Sanderson-SmithUNKNOWN M Protein Study Group
Jul 15, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rasmus MortensenJes Dietrich

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Methods Mentioned

BETA
peptide array
ELISA
biopsies
peptide array technology
chip

Software Mentioned

GraphPad Prism
GraphPad
pSORT
BLAST
TMpred

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