Identification of in vivo expressed vaccine candidate antigens from Staphylococcus aureus

Proc Natl Acad Sci U S A. 2002 May 14;99(10):6573-8. doi: 10.1073/pnas.092569199. Epub 2002 May 7.

Abstract

For the design of potent subunit vaccines, it is of paramount importance to identify all antigens immunologically recognized by a patient population infected with a pathogen. We have developed a rapid and efficient procedure to identify such commonly recognized antigens, and here we provide a comprehensive in vivo antigenic profile of Staphylococcus aureus, an important human pathogen. S. aureus peptides were displayed on the surface of Escherichia coli via fusion to one of two outer membrane proteins (LamB and FhuA) and probed with sera selected for high Ab titer and opsonic activity. A total of 60 antigenic proteins were identified, most of which are located or predicted to be located on the surface of the bacterium or secreted. The identification of these antigens and their reactivity with individual sera from patients and healthy individuals greatly facilitate the selection of promising vaccine candidates for further evaluation. This approach, which makes use of whole genome sequence information, has the potential to greatly accelerate and facilitate the formulation of novel vaccines and is applicable to any pathogen that induces Abs in humans and/or experimental animals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology*
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / immunology
  • Base Sequence
  • DNA, Bacterial
  • Epitopes, B-Lymphocyte / immunology
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / immunology
  • Gene Expression
  • Genome, Bacterial
  • Genomic Library
  • Humans
  • Macrophages / immunology
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Phagocytosis
  • Porins
  • Receptors, Virus / genetics
  • Receptors, Virus / immunology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Staphylococcal Infections / blood
  • Staphylococcal Infections / immunology*
  • Staphylococcal Vaccines / genetics
  • Staphylococcal Vaccines / immunology*
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / immunology
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology*

Substances

  • Antigens, Bacterial
  • Bacterial Outer Membrane Proteins
  • DNA, Bacterial
  • Epitopes, B-Lymphocyte
  • Escherichia coli Proteins
  • FhuA protein, E coli
  • Porins
  • Receptors, Virus
  • Recombinant Fusion Proteins
  • Staphylococcal Vaccines
  • Vaccines, Synthetic
  • maltoporins