Plaque reduction neutralization assays, using foot-and-mouth disease virus (FMDV) type A, strain 119 and immune serum from convalescent guinea-pigs infected with this strain of virus and performed with monolayers of a swine kidney cell line, resulted in biphasic neutralization curves because of the presence of as many as 30 to 50% of non-neutralized virus particles at peak activity. These results were found using gum tragacanth, agar, agar containing DEAE-dextran, and methylcellulose overlays and were also found using monolayers of guinea-pig embryo tongue and guinea-pig embryo heelpad cells. Non-neutralized virus in immune serum-FMDV mixtures was neutralized after the addition of anti-species antibody, demonstrating that the non-neutralized virus fraction consisted of virus in the form of infectious immune complexes. These complexes were not infectious when inoculated intraperitoneally into suckling mice or intracardially into guinea-pigs. They were infectious, however, if inoculated intradermally into the tongue or rear heelpads of guinea-pigs. Low doses of passively transferred immune serum did not protect guinea-pigs against the formation of primary vesicles after intradermal tongue or heelpad challenge with virus but did protect against systemic spread of virus to the remaining uninoculated feet. Higher doses of passively transferred immune serum protected against tongue challenge but even higher doses were required to protect against heelpad challenge. The role of antibody in protection against the systemic spread of FMDV may be due to infectious immune complexes being removed from the blood by the reticuloendothelial system. In the dermis of the tongue and heelpad, the immune complexes remain infectious, resulting in the formation of local vesicles except when these tissues contain very high concentrations of antibody.


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