Synergistic interactions of antibodies in rate of virus neutralization

Antibodies and antibody combinations are often evaluated only by their potency in inactivating a known quantity of virus in dose-effect assays. However, a crucial additional parameter is the rate at which neutralization takes place, or kinetics. Synergism of certain antibody combinations in dose-effect 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 neutralization kinetics. To determine whether synergism in dose-effect assays can predict synergism in neutralization rate, the ability of neutralizing antibodies to synergize in neutralization rate (kinetics) was compared to their ability to synergize in dose-effect assays (potency) in cell-free assays. Although certain antibody combinations synergized in both neutralization rate and potency, combinations that did not clearly synergize in potency could still significantly synergize in neutralization rate. Weak neutralizing antibodies could also greatly increase the neutralization rate of more potent antibodies. These results suggest that evaluating antibody combinations in dose-effect assays but not in neutralization kinetics provides a partial picture of neutralizing antibody dynamic interactions and may prevent the identification of certain favorable antibody combinations. These findings also support the importance of establishing defined antibody cocktails for prophylactic and therapeutic purposes. A simple strategy to evaluate antibody interactions in neutralization kinetics is proposed in which a quantitative prediction of additivity is made on the basis of the neutralization rate constants of the individual antibodies in the combination.