title: Neutralization of poliovirus by a monoclonal antibody: kinetics and stoichiometry.
abstract: First-order kinetics of neutralization have usually been interpreted as evidence that a single antibody, binding at a critical site, neutralizes the infectivity of a virus particle. In such a case, if all the binding sites were critical, an average of one antibody bound per virion would be required to reduce the infectivity of a virus sample to 37% (1/e) of its initial infectivity. However, in the work reported here using a monoclonal antibody to poliovirus which inactivated with first-order kinetics, an average of four bound antibodies were required. These results are consistent with two different models: one in which only one-fourth of the antibody binding sites on the virion are critical for neutralization; the other, in which none of the sites is critical, but neutralization takes place instead in a stepwise fashion in which each bound antibody reduces the infectivity by a factor of 3/4. The maximum binding capacity of the virion for this monoclonal antibody was approximately 30 molecules. Since the 60 protein subunits of the poliovirus capsid are related by 30 twofold axes of symmetry, it is proposed that each monoclonal antibody binds bivalently to two protein subunits related by a twofold axis. Such a binding mode would crosslink pentamers, the basic structures in picornaviral assembly and dissociation. It is proposed that pentamer crosslinking is an important element in neutralization by this monoclonal antibody. Another antibody, which may neutralize by a different mechanism, is also discussed briefly.
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D001666:Binding Sites, Antibody; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007700:Kinetics; D008954:Models, Biological; D009500:Neutralization Tests; D017955:Poliovirus / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D007140:Immunoglobulin Fab Fragments