Multiple variants in foot-and-mouse disease virus (FMDV) populations: the Achilles heel for peptide and rec. DNA vaccines?

Variants of type A10 FMDV were isolated by passage of virus in BHK-cells in the presence of a neutralizing anti-peptide serum or monoclonal antibodies. These variants which were no longer neutralized by the particular anti-peptide serum or monoclonal antibody were easily obtained from (crude) virus populations ("cattle" virus and BHK-adapted virus). The rapidity of isolation (in two or three passages) suggested that these variants are already present in normal virus populations. All (plaque purified) variants isolated so far seem to be different: A panel of 20 monoclonal antibodies and an anti-peptide serum showed different neutralization patterns for all isolates and parent virus. Electrofocusing patterns of many variants were found to be different showing changed charges for VP2 as well as for VP1. Thus in FMDV both VP1 and VP2 are probably involved in antigenic sites. Normally the variants escape our attention because in neutralization assays only a limited quantity of infective units are used, representing only the "top of the iceberg". In classical inactivated virus vaccines many of these variants will be represented and therefore can be expected to be "primed" immunogenetically. This will not be the case with peptide vaccines or in case of recombinant DNA products, where only one virus clone is represented. In addition, and probably more important, inactivated virus vaccines will raise antibodies against completely independent epitopes that each have a limited chance to be changed in the variants present in the challenge virus population. Thus if peptide vaccines can be composed in such a way that antibodies are raised against completely different antigenic sites the chance of break through of variants will be strongly limited and it is expected that the efficient protection of inactivated virus vaccines can be approached.