EFFICIENT NEUTRALIZATION OF FOOT-AND-MOUTH-DISEASE VIRUS BY MONOVALENT ANTIBODY-BINDING

Neutralization of an aphthovirus by monovalent binding of an antibody is reported. Foot-and-mouth disease virus (FMDV) clone C-S8c1 was neut ralized by monoclonal antibody (MAb) SD6, which was directed to a cont inuous epitope within a major antigenic site of the G-H loop of capsid protein VP1. On a molar basis, the Fab fragment was at most fivefold less active in neutralization than the intact antibody, and both block ed virus attachment to cells. Neither the antibody nor the Fab fragmen t caused aggregation of virions, as evidenced by sucrose gradient sedi mentation studies of the antibody-virus complex formed at antibody to virion ratios of 1:50 to 1:10,000. The results of neutralization of in fectivity and of ultracentrifugation are fully consistent with structu ral data based on X-ray crystallographic and cryoelectron microscopy s tudies, which showed monovalent interaction of the antibody with a cri tical receptor binding motif Arg-Gly-Asp. The conclusions of these neu tralization studies are that (i) bivalent binding of antibody is not a requisite for strong neutralization of aphthoviruses and (ii) aggrega tion of viral particles, which has been proposed to be the dominant ne utralization mechanism of antibodies that bind monovalently to virions , is not necessary for the neutralization of FMDV C-S8c1 by MAb SD6.