Neutralizing epitopes of type O foot-and-mouth disease virus. I. Identification and characterization of three functionally independent, conformational sites.
Eleven neutralizing monoclonal antibodies (MAbs) were produced to the O1BFS 1860/67 strain of foot-and-mouth disease virus (FMDV), and were characterized for their ability to bind viral and subviral antigens in different ELISA tests and to neutralize heterologous type O isolates. Neutralization escape variants of the homologous virus, isolated under pressure from five of these MAbs, were used in cross-neutralization tests with all of the 11 antibodies. These studies identified three functionally independent, conformational, neutralizing sites. The most conformationally dependent site bound antibody which neutralized a range of type O virus isolates. A second site was less dependent on conformation and was recognized by antibody that was strain-specific. The least conformational site bound MAbs which showed limited cross-neutralization of other type O strains. This latter site appeared to be immunodominant and contained several overlapping epitopes which showed some differences in their specificities. Isoelectrofocusing and sequencing studies of the variants strongly suggested that polypeptide VP2 contributes to the immunodominant site.
Barnett
P V
PV
Department of Virology, Wellcome Biotechnology Ltd, Beckenham, Kent, U.K.
Ouldridge
E J
EJ
Rowlands
D J
DJ
Brown
F
F
Parry
N R
NR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000302:isolation & purification; D000914:Antibodies, Viral / Q000276:immunology; D000918:Antibody Specificity; D000956:Antigens, Viral / Q000032:analysis / Q000276:immunology*; D005537:Aphthovirus / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000032:analysis / Q000276:immunology; D007525:Isoelectric Focusing; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D012367:RNA, Viral / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D012367:RNA, Viral