Antigenic determinants of vesicular stomatitis virus: analysis with antigenic variants

Antigenic variants of vesicular stomatitis virus (VSV) serotypes New Jersey and Indiana (VSV-NJ, VSV-Ind) were selected by using a panel of monoclonal antibodies (MAb) specific for the major surface glycoprotein (G-protein). The reactivity of antigenic variants with the panel of MAb confirmed observations made by competitive binding assays that four distinct antigenic sites (A-D)NJ on the VSV-NJ G-protein and four partially overlapping sites (A, B1, B2, C)Ind on the VSV-Ind G-protein are involved in virus neutralization. Furthermore, subregions within the A epitopes of both serotypes were detected by variant analysis. The frequency of variation at most epitopes was 1 in 10(5) for VSV-NJ and 1 in 10(6) for VSV-Ind. The A3 and C determinants of VSV-Ind, however, defined by MAb that exhibited overlap in binding to other epitopes, appeared to be relatively invariant. Multiple mutations may be necessary to abolish antibody binding at these sites. Overlap of the C group of anti-VSV-Ind MAb with the A epitopes was assigned to the A2 subregion, because variants selected with A2 MAb show reduced binding of C MAb. Heterogeneous antisera from a primary immune response could detect differences in reactivity between variants at the A epitopes and wild-type VSV-NJ or VSV-Ind, suggesting the A epitope is immunodominant. Hyperimmune sera could detect a small difference between ANJ and BNJ variants compared to wild-type VSV-NJ, but could not distinguish between VSV-Ind variants and wild-type VSV-Ind.