Negative selection on neutralization epitopes of poliovirus surface proteins: implications for prediction of candidate epitopes for immunization

Gene. 2004 Mar 17;328:127-33. doi: 10.1016/j.gene.2003.11.020.

Abstract

For development of effective vaccines against viruses, it is of importance to choose appropriate epitopes as the target for immunization. These epitopes should eventually be determined experimentally, but it would be helpful if we could predict candidate epitopes computationally because it accelerates the entire process. To predict candidate epitopes for immunization, it is of great interest to characterize the target epitopes of poliovirus vaccine, which has empirically proven to be the most effective among all vaccines available. Here I show that almost all amino acid sites of poliovirus surface proteins VP1, VP2, and VP3 including neutralization epitopes are negatively selected and no site is under positive selection. These results, together with those obtained in previous studies, indicate that vaccines directed against epitopes, which consist of negatively selected sites protect vaccinees more effectively than those directed against epitopes which contain positively selected sites. These observations suggest that candidate epitopes for immunization are predicted by the molecular evolutionary analysis of viral protein (and its coding nucleotide) sequences, as the epitopes which consist exclusively of negatively selected amino acid sites.

MeSH terms

  • Amino Acids / genetics
  • Amino Acids / immunology
  • Capsid Proteins / genetics
  • Capsid Proteins / immunology*
  • Databases, Nucleic Acid
  • Epitope Mapping / methods
  • Epitopes / genetics
  • Epitopes / immunology*
  • Neutralization Tests
  • Poliovirus / genetics
  • Poliovirus / immunology*
  • Poliovirus Vaccines / genetics
  • Poliovirus Vaccines / immunology
  • Reproducibility of Results
  • Selection, Genetic

Substances

  • Amino Acids
  • Capsid Proteins
  • Epitopes
  • Poliovirus Vaccines
  • VP1 protein, Poliovirus
  • VP2 protein, Poliovirus
  • VP3 protein, Poliovirus