Conserved anchorless surface proteins as group A streptococcal vaccine candidates

J Mol Med (Berl). 2012 Oct;90(10):1197-207. doi: 10.1007/s00109-012-0897-9. Epub 2012 Apr 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Bacterial Proteins / immunology
  • Bacterial Proteins / metabolism*
  • Cell Wall / immunology
  • Cell Wall / metabolism*
  • Child
  • Female
  • Humans
  • Hydrolases / immunology
  • Hydrolases / metabolism*
  • Immune Sera / immunology
  • Immunity, Active
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Microscopy, Immunoelectron
  • Peptidylprolyl Isomerase / immunology
  • Peptidylprolyl Isomerase / metabolism*
  • Proteome / immunology
  • Proteome / metabolism
  • Rabbits
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism
  • Streptococcal Infections / immunology
  • Streptococcal Infections / prevention & control*
  • Streptococcal Vaccines / administration & dosage
  • Streptococcal Vaccines / immunology
  • Streptococcal Vaccines / metabolism*
  • Streptococcus pyogenes / enzymology
  • Streptococcus pyogenes / immunology*
  • Streptococcus pyogenes / ultrastructure
  • Vaccination
  • Young Adult


  • Bacterial Proteins
  • Immune Sera
  • Proteome
  • Recombinant Proteins
  • Streptococcal Vaccines
  • Hydrolases
  • arginine deiminase
  • Peptidylprolyl Isomerase