High and low efficiency neutralization epitopes on the haemagglutinin of type A influenza virus

The relationship between the efficiency of the neutralization process and the affinity of five monoclonal IgG antibodies specific for the haemagglutinin of type A influenza virus has been investigated by determining their neutralization rate constants (Kneut.) and affinities (Kdissoc.). We addressed the hypothesis that if antibody affinity alone determined the efficiency of neutralization, then the Kneut.:Kdissoc. ratio would be the same for all antibodies. However, we found that the Kneut.:Kdissoc. ratio varied by up to 125-fold, suggesting that properties unique to the epitope are of major importance in determining the efficiency of neutralization. These data suggest that vaccines should preferentially stimulate antibodies to epitopes that mediate the most efficient neutralization, and that a high Kdissoc. should be an important but secondary consideration.