Post-attachment neutralization of HPV16 by antibodies derived from Gardasil-vaccinated women

HPV vaccines exhibit high type-specific and antibody-mediated protection against anogenital infection, even after a single dose. Complete and long-term "sterilizing" immunity against incident infection appears to be established in most HPV vaccinees, suggesting that not only are persistent levels of virus-inhibiting antibodies routinely generated but that they are also exceptionally potent at preventing infection. The process of HPV infection is unusually protracted at several steps, including slow internalization after the virions bind to the cell surface. This observation prompted us to comprehensively evaluate the ability of neutralizing antibodies to prevent infection subsequent to HPV pseudovirion attachment to cells. Using sera and memory B cell-derived monoclonal antibodies from Gardasil-vaccinated women, we observed almost complete post-attachment neutralization of HPV16 pseudovirion infection of HaCaT cells three hours after attachment, even when vaccinees' sera were diluted 250-fold, with a gradual loss of activity up to 18 h. Unexpectedly, three distinct mechanisms of post-attachment neutralization were discovered, capsid shedding from the cell surface, capsid retention on the cell surface, and rapid capsid degradation after internalization.