Synergistic interactions of antibodies in rate of virus neutralization

Antibodies and antibody combinations are often evaluated only by their pote ncy in inactivating a known quantity of virus in dose-effect assays. Howeve r, a crucial additional parameter is the rate at which neutralization takes place, or kinetics. Synergism of certain antibody combinations in dose-eff ect assays has been previously demonstrated. In the present report, using a battery of murine monoclonal antibodies to herpes simplex virus (HSV], we investigated whether antiviral antibodies can also synergize in neutralizat ion kinetics. To determine whether synergism in dose-effect assays can pred ict synergism in neutralization rate, the ability of neutralizing antibodie s to synergize in neutralization rats (kinetics) was compared to their abil ity to synergize in dose-effect assays (potency) in cell-free assays. Altho ugh certain antibody combinations synergized in both neutralization rate an d potency, combinations that did not clearly synergize in potency could sti ll significantly synergize in neutralization rate. Weak neutralizing antibo dies could also greatly increase the neutralization rate of more potent ant ibodies. These results suggest that evaluating antibody combinations in dos e-effect assays but not in neutralization kinetics provides a partial pictu re of neutralizing antibody dynamic interactions and may prevent the Identi fication of certain favorable antibody combinations. These findings also su pport the importance of establishing defined antibody cocktails for prophyl actic and therapeutic purposes. A simple strategy to evaluate antibody inte ractions In neutralization kinetics is proposed in which a quantitative pre diction of additivity Is made on the basis of the neutralization rate const ants of the individual antibodies in the combination. (C) 2000 Academic Pre ss.