The reaction of foot-and-mouth disease virus (FMDV) with 12S subunit/140S virion cross-reactive (sensitizing) antibody was studied in order to elucidate the requirements for neutralization versus sensitization. The presence of sensitizing antibody in immune serum caused an atypical neutralization response curve and a non-neutralized fraction. Cell-associated (cytophilic) antibody was not present in the system. Dissociation of the immune complex was not a factor and sensitized virus adsorbed to host cells via the regular virus receptor site(s). This finding led to the conclusion that sensitizing antibody is specific for non-critical sites. Dosing of the neutralization reaction mixtures with fractionated antibody of alternative antigenic specificities had an antagonistic effect on the neutralization response, suggesting steric hindrance. Cell receptor sites were a factor in sensitization since different host systems had different susceptibilities for sensitized antigen. The results suggest that neutralization of FMDV requires the attachment of multiple antibody molecules as proposed by the multi-hit theory of neutralization. The measurement of serum neutralizing activity as an indication of the immune response is discussed.


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