Mechanism of neutralization of influenza virus infectivity by antibodies.

We have determined the mechanism of neutralization of influenza virus infectivity by three antihemagglutinin monoclonal antibodies, the structures of which we have analyzed before as complexes with hemagglutinin. The antibodies differ in their sites of interaction with hemagglutinin and in their abilities to interfere in vitro with its two functions of receptor binding and membrane fusion. We demonstrate that despite these differences all three antibodies neutralize infectivity by preventing virus from binding to cells. Neutralization occurs at an average of one antibody bound per four hemagglutinins, a ratio sufficient to prevent the simultaneous receptor binding of hemagglutinins that is necessary to attach virus to cells.