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The in vitro interaction of foot-and-mouth disease virus (FMDV) with an immune serum resulted in a fraction of virus which failed to be neutralized. This inability of antibody to neutralize the entire population of a virus preparation was studied with emphasis on the antigenic specificity of the antibody-virus reaction. Antibody to FMDV recognized multiple antigenic determinants. Immunoabsorbent fractionation of the serum into 12S subunit cross-reactive and 140S virion-specific antibody revealed that these multiple antigenic determinants are factors in determining the neutralizing ability of the antibody. Antibody specific to the infective 140S virion neutralized virus effectively, whereas antibody reactive with both the 140S virion and 12S non-infective component did so ineffectively. Neutralization was independent of viral aggregation, strain, or type heterogeneity, dissociation of the immune complex, heterogeneity of antibody class, or incubation time. The non-neutralized fraction of virus was not due to insufficient antibody in the system, was demonstrated to be complexed with antibody ('sensitized') and could be neutralized with anti-globulin serum. The findings demonstrate the heterogeneity of antibody specificity of FMDV in serum preparations and relate the importance of antibody specificity to the neutralization of virus in vitro.

Neutralization of Foot-and-Mouth Disease Virus. I. Sensitization of the 140S Virion by Antibody Also Reactive with the 12S Protein Subunit