Conserved anchorless surface proteins as group A streptococcal vaccine candidates
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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.
KeywordsStreptococcus pyogenes Arginine deiminase Trigger factor Vaccine
Acknowledgements and disclosure statement
The authors wish to thank M. Caparon for providing the HSC5 GAS strain, M. Kotb for providing the 20174 GAS strain, and B. Currie for providing Aboriginal serum. A.H. is a recipient of an Australian Postgraduate Award and a DAAD Research Grant for Doctoral Candidates, Young Academics and Scientists. A.J.C. is a recipient of a University of Wollongong Postgraduate Award. J.N.C. is the recipient of a National Health and Medical Research Council of Australia (NHMRC) Overseas Biomedical Fellowship. This work was supported by the NHMRC (M.J.W., B.K. and M.R.B.) and a DEST International Science Linkages Grant (M.J.W. and V.N.). B.K. and M.J.W. are NHMRC Research Fellows. The authors (A.H., E.C., J.N.C., C.M.G., V.R., K.S.S., I.Y.R.M., M.R.B., and M.J.W.) have an intellectual property or commercial interest in the antigens described in this study.
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