Characterization and identification of vaccine candidate proteins through analysis of the group A Streptococcus surface proteome

Nat Biotechnol. 2006 Feb;24(2):191-7. doi: 10.1038/nbt1179. Epub 2006 Jan 15.


We describe a proteomic approach for identifying bacterial surface-exposed proteins quickly and reliably for their use as vaccine candidates. Whole cells are treated with proteases to selectively digest protruding proteins that are subsequently identified by mass spectrometry analysis of the released peptides. When applied to the sequenced M1_SF370 group A Streptococcus strain, 68 PSORT-predicted surface-associated proteins were identified, including most of the protective antigens described in the literature. The number of surface-exposed proteins varied from strain to strain, most likely as a consequence of different capsule content. The surface-exposed proteins of the highly virulent M23_DSM2071 strain included 17 proteins, 15 in common with M1_SF370. When 14 of the 17 proteins were expressed in E. coli and tested in the mouse for their capacity to confer protection against a lethal dose of M23_DSM2071, one new protective antigen (Spy0416) was identified. This strategy overcomes the difficulties so far encountered in surface protein characterization and has great potential in vaccine discovery.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Bacterial / analysis
  • Antigens, Bacterial / chemistry
  • Antigens, Bacterial / immunology
  • Bacterial Vaccines / analysis*
  • Bacterial Vaccines / chemistry
  • Bacterial Vaccines / immunology*
  • Bacterial Vaccines / therapeutic use
  • Drug Delivery Systems / methods
  • Drug Design
  • Mass Spectrometry / methods
  • Membrane Proteins / analysis*
  • Membrane Proteins / chemistry
  • Membrane Proteins / immunology*
  • Mice
  • Molecular Sequence Data
  • Peptide Mapping / methods
  • Proteome / analysis*
  • Proteome / chemistry
  • Proteome / immunology
  • Streptococcal Infections / immunology*
  • Streptococcal Infections / prevention & control
  • Streptococcus pyogenes / immunology
  • Streptococcus pyogenes / metabolism*


  • Antigens, Bacterial
  • Bacterial Vaccines
  • Membrane Proteins
  • Proteome