Conserved anchorless surface proteins as group A streptococcal vaccine candidates.
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Authors
Henningham, AnnaChiarot, Emiliano
Gillen, Christine M
Cole, Jason N
Rohde, Manfred
Fulde, Marcus
Ramachandran, Vidiya
Cork, Amanda J
Hartas, Jon
Magor, Graham
Djordjevic, Steven P
Cordwell, Stuart J
Kobe, Bostjan
Sriprakash, Kabada S
Nizet, Victor
Chhatwal, G S
Margarit, Immaculada Y R
Batzloff, Michael R
Walker, Mark J
Issue Date
2012-10
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Show full item recordAbstract
Streptococcus pyogenes (group A Streptococcus (GAS)) causes ∼700 million human infections each year, resulting in over 500,000 deaths. The development of a commercial GAS vaccine is hampered by the occurrence of many unique GAS serotypes, antigenic variation within the same serotype, differences in serotype geographical distribution, and the production of antibodies cross-reactive with human tissue that may lead to autoimmune disease. Several independent studies have documented a number of GAS cell wall-associated or secreted metabolic enzymes that contain neither N-terminal leader sequences nor C-terminal cell wall anchors. Here, we applied a proteomic analysis of serotype M1T1 GAS cell wall extracts for the purpose of vaccine development. This approach catalogued several anchorless proteins and identified two protective vaccine candidates, arginine deiminase and trigger factor. These surface-exposed enzymes are expressed across multiple GAS serotypes exhibiting ≥99% amino acid sequence identity. Vaccine safety concerns are alleviated by the observation that these vaccine candidates lack human homologs, while sera from human populations suffering repeated GAS infections and high levels of autoimmune complications do not recognize these enzymes. Our study demonstrates anchorless cell surface antigens as promising vaccine candidates for the prevention of GAS disease.Citation
Conserved anchorless surface proteins as group A streptococcal vaccine candidates. 2012, 90 (10):1197-207 J. Mol. Med.Affiliation
School of Biological Sciences, University of Wollongong, Wollongong, NSW, 2522, Australia.PubMed ID
22527883Type
ArticleLanguage
enISSN
1432-1440ae974a485f413a2113503eed53cd6c53
10.1007/s00109-012-0897-9
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