Efficient neutralization of foot-and-mouth disease virus by monovalent antibody binding

Abstract

Neutralization of an aphthovirus by monovalent binding of an antibody is reported. Foot-and-mouth disease virus (FMDV) clone C-S8c1 was neutralized by monoclonal antibody (MAb) SD6, which was directed to a continuous 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 blocked virus attachment to cells. Neither the antibody nor the Fab fragment caused aggregation of virions, as evidenced by sucrose gradient sedimentation studies of the antibody-virus complex formed at antibody to virion ratios of 1:50 to 1:10,000. The results of neutralization of infectivity and of ultracentrifugation are fully consistent with structural data based on X-ray crystallographic and cryoelectron microscopy studies, which showed monovalent interaction of the antibody with a critical receptor binding motif Arg-Gly-Asp. The conclusions of these neutralization studies are that (i) bivalent binding of antibody is not a requisite for strong neutralization of aphthoviruses and (ii) aggregation of viral particles, which has been proposed to be the dominant neutralization mechanism of antibodies that bind monovalently to virions, is not necessary for the neutralization of FMDV C-S8c1 by MAb SD6.

Comparison of Two Single-Chain Antibodies That Neutralize Canine Parvovirus: Analysis of an Antibody-Combining Site and Mechanisms of Neutralization

“…This is the first study to investigate the details of the antibody-binding and neutralization mechanisms of parvoviruses. The mechanisms are generally similar to those reported for the neutralization of other nonenveloped and enveloped viruses, indicating that there are only a limited number of processes of neutralization for most viruses (Outlaw and Dimmock, 1991;Smith, 1993;Verdaguer et al, 1997;Che et al, 1998;Fleury et al, 1999;Sattentau et al, 1999;Smith and Baker, 1999).…”

“…The interactions involve antibody binding to the viral structures in a number of different ways, including binding to flexible loops (Logan et al, 1993;Verdaguer et al, 1999) or to structures that are determined by the folded polypeptide (Colman et al, 1987;Malby et al, 1993;Bizebard et al, 1995;Che et al, 1998;Malby et al, 1998). The mechanisms of virus neutralization can include virus aggregation, masking of receptor attachment sites, steric inhibition of receptor binding, or stabilization of the capsid to inhibit virus uncoating (Outlaw and Dimmock, 1991;Smith, 1993;Verdaguer et al, 1997;Fleury et al, 1999;Sattentau et al, 1999;Smith and Baker, 1999).…”

A Similar Pattern of Interaction for Different Antibodies with a Major Antigenic Site of Foot-and-Mouth Disease Virus: Implications for Intratypic Antigenic Variation

“…This structure revealed that the RGD triplet participates directly in the interaction with antibody SD6 (52,53). Cryoelectron microscopy (18) and biochemical (51) studies have shown that SD6 is an effective neutralizer that binds monovalently to particles without causing aggregation of virions. Antibody SD6 neutralizes by blocking attachment of virus particles to cells (51).…”

“…Cryoelectron microscopy (18) and biochemical (51) studies have shown that SD6 is an effective neutralizer that binds monovalently to particles without causing aggregation of virions. Antibody SD6 neutralizes by blocking attachment of virus particles to cells (51). A dual participation of capsid amino acids in receptor recognition and antibody binding has recently been observed also for poliovirus (15) and rhinovirus (47).…”

Passive Immunisierung bei Hund und Katze

“…Antikörper binden spezifisch an Oberflächenantigene von Erregern, um diese zu neutralisieren und als "fremd" zu markieren (Opsonisierung). Die Anhef-tung des Erregers an die Zielzellen und damit dessen Vermehrung wird vermieden und die klinische Manifestation der Erkrankung verhindert (41).…”