Monoclonal antibodies to an Indian strain of type a foot-and-mouth diseasevirus

A set of five neutralizing monoclonal antibodies (MAbs) to an Indian strain (IND 17/77) of type A (subtype A22) foot-and-mouth disease (FMD) virus (FM DV) was used in the study. Four of the MAbs (275, 37S, 85S, and 143S) ident ified a trypsin-sensitive (TS) epitope(s) and were specific for VP1,while t he remaining MAb (145S) reacted with a trypsin-resistant (TR) epitope and w as specific for VP3 in Western blot analysis. Both the epitopes (TS and TR) were conformation-independent in nature. Results obtained in MAb-competiti on enzyme-linked immunosorbent assay (ELISA), and profiling of the (MAb) ne utralization-escape mutants in ELISA and cross-neutralization test revealed two overlapping TS epitopes (27S/37S and 85S/143S) on the virus. Variation at both these epitopes was observed in some field isolates of serotype A. Comparison of deduced amino acid sequence in the VP1 region (aa 140-213) be tween the parent virus and the mutants identified Gly(148) and Arg(153) as critical for the formation of both the TS epitopes. Substitution of R-153 b y Gly or Ser was observed in mutants with no reactivity for the MAbs 85S/14 3S. However, these mutants maintained partial reactivity with MAbs 27S/37S, and substitution of GlY(148) by Glu eliminated both the epitopes. No amino acid substitution was observed in the VPI region of aa 200-213. Efficient neutralization of the MAb neutralization escape mutants (MAb-resistant (MAR ) mutants) by bovine vaccinate serum (BVS) indicated involvement of other e pitopes on the virion surface in eliciting neutralizing antibodies followin g vaccination.