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Journal of Molecular Medicine

, Volume 90, Issue 10, pp 1197–1207 | Cite as

Conserved anchorless surface proteins as group A streptococcal vaccine candidates

  • Anna Henningham
  • Emiliano Chiarot
  • Christine M. Gillen
  • Jason N. Cole
  • Manfred Rohde
  • Marcus Fulde
  • Vidiya Ramachandran
  • Amanda J. Cork
  • Jon Hartas
  • Graham Magor
  • Steven P. Djordjevic
  • Stuart J. Cordwell
  • Bostjan Kobe
  • Kabada S. Sriprakash
  • Victor NizetEmail author
  • G. S. Chhatwal
  • Immaculada Y. R. Margarit
  • Michael R. Batzloff
  • Mark J. WalkerEmail author
Original Article

Abstract

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.

Keywords

Streptococcus pyogenes Arginine deiminase Trigger factor Vaccine 

Notes

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.

Supplementary material

109_2012_897_MOESM1_ESM.pdf (61 kb)
Supplementary Table 1 Peptide mass fingerprinting identification of cell wall-associated proteins of S. pyogenes isolate 5448 and percent identity of cell wall-associated proteins with human homologs (PDF 60 kb)

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Anna Henningham
    • 1
    • 2
  • Emiliano Chiarot
    • 3
  • Christine M. Gillen
    • 1
    • 4
  • Jason N. Cole
    • 1
    • 5
  • Manfred Rohde
    • 4
  • Marcus Fulde
    • 4
  • Vidiya Ramachandran
    • 1
  • Amanda J. Cork
    • 1
  • Jon Hartas
    • 6
  • Graham Magor
    • 6
  • Steven P. Djordjevic
    • 7
  • Stuart J. Cordwell
    • 8
  • Bostjan Kobe
    • 2
    • 9
  • Kabada S. Sriprakash
    • 6
  • Victor Nizet
    • 5
    Email author
  • G. S. Chhatwal
    • 4
  • Immaculada Y. R. Margarit
    • 3
  • Michael R. Batzloff
    • 6
    • 10
  • Mark J. Walker
    • 1
    • 2
    Email author
  1. 1.School of Biological SciencesUniversity of WollongongWollongongAustralia
  2. 2.School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research CentreUniversity of QueenslandBrisbane St LuciaAustralia
  3. 3.Research Center, Novartis Vaccines and DiagnosticsSienaItaly
  4. 4.Department of Medical MicrobiologyHelmholtz Centre for Infection ResearchBraunschweigGermany
  5. 5.Department of PediatricsUniversity of California San DiegoLa JollaUSA
  6. 6.The Queensland Institute of Medical ResearchPost Office Royal Brisbane HospitalBrisbaneAustralia
  7. 7.The ithree InstituteUniversity of Technology SydneySydneyAustralia
  8. 8.School of Molecular and Microbial BiosciencesUniversity of SydneySydneyAustralia
  9. 9.Division of Chemistry and Structural Biology, Institute for Molecular BioscienceUniversity of QueenslandSt LuciaAustralia
  10. 10.Institute for GlycomicsGriffith UniversitySouthportAustralia

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