Analysis of neutralizing epitopes on foot-and-mouth disease virus.
For the investigation of the antigenic determinant structure of foot-and-mouth disease virus (FMDV), neutralizing monoclonal antibodies (MAbs) against complete virus were characterized by Western blot (immunoblot), enzyme immunoassay, and competition experiments with a synthetic peptide, isolated coat protein VP1, and viral particles as antigens. Two of the four MAbs reacted with each of these antigens, while the other two MAbs recognized only complete viral particles and reacted only very poorly with the peptide. The four MAbs showed different neutralization patterns with a panel of 11 different FMDV strains. cDNA-derived VP1 protein sequences of the different strains were compared to find correlations between the primary structure of the protein and the ability of virus to be neutralized. Based on this analysis, it appears that the first two MAbs recognized overlapping sequential epitopes in the known antigenic site represented by the peptide, whereas the two other MAbs recognized conformational epitopes. These conclusions were supported and extended by structural analyses of FMDV mutants resistant to neutralization by an MAb specific for a conformational epitope. These results demonstrate that no amino acid exchanges had occurred in the primary antigenic site of VP1 but instead in the other coat proteins VP2 and VP3, which by themselves do not induce neutralizing antibodies.
Pfaff
E
E
Microbiology and Zentrum für Molekulare Biologie Heidelberg, University of Heidelberg, Federal Republic of Germany.
Thiel
H J
HJ
Beck
E
E
Strohmaier
K
K
Schaller
H
H
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D005537:Aphthovirus / Q000276:immunology*; D002213:Capsid / Q000276:immunology; D007163:Immunosorbent Techniques; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D009842:Oligopeptides