Identification of a fifth neutralizable site on type O foot-and-mouth disease virus following characterization of single and quintuple monoclonal antibody escape mutants

J Gen Virol. 1993 Aug:74 ( Pt 8):1547-53. doi: 10.1099/0022-1317-74-8-1547.

Abstract

A monoclonal antibody (C3) produced against foot-and-mouth disease virus type O1Caseros was found to neutralize quadrivalent monoclonal antibody escape mutant (G67) of foot-and-mouth disease virus type O1Kaufbeuren. This mutant had been characterized at the sequence level as having distinct changes affecting four non-overlapping neutralizable sites. The C3 monoclonal antibody was used to prepare a quintuple escape mutant from the G67 and a single escape mutant from the parental O1Kaufbeuren viruses. Polyclonal post-vaccinated and infected cattle sera as well as polyclonal mouse and guinea-pig sera, which neutralized the quadrivalent mutant, no longer neutralized the quintuple mutant, indicating that a fifth site had been identified and that changing the fifth site eliminated all neutralization. The site was characterized using serological techniques and found to be conformationally dependent, trypsin-sensitive and independent of sites previously characterized by monoclonal antibodies. Amino acid sequencing comparing parental, single C3 and quintuple mutants showed that a single change from a glutamine to a histidine, at amino acid 149 in the structural protein VP1, (1D) characterized the C3 mutation. The fifth site probably represents a conformational epitope which is formed due to the interaction of the VP1 loop region with other surface amino acids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology*
  • Aphthovirus / genetics
  • Aphthovirus / immunology*
  • Cattle
  • Enzyme-Linked Immunosorbent Assay
  • Guinea Pigs
  • Molecular Sequence Data
  • Mutation / immunology*
  • Neutralization Tests
  • Rabbits
  • Viral Proteins / genetics
  • Viral Proteins / immunology*

Substances

  • Antibodies, Monoclonal
  • Antigens, Viral
  • Viral Proteins