Opportunities to exploit non-neutralizing HIV-specific antibody activity.

Antibodies act as a nexus between innate and adaptive immunity: they provide a means to engage a spectrum of innate immune effector cells in order to clear viral particles and infected cells and prime antigen presentation. This functional landscape is remarkably complex, and depends on antibody isotype, subclass, and glycosylation; the expression levels and patterns of a suite of Fc receptors with both complementary and opposing activities; and a host of innate immune cells capable of differential responses to opsonized particles and present at different sites. In vivo, even neutralizing antibodies rely on their ability to act as molecular beacons and recruit innate immune effector cells in order to provide protection, and results from both human and macaque studies have implicated these effector functions in vaccinemediated protection. Thus, while enhancing effector function is a tractable handle for potentiating antibody-mediated protection from HIV infection, success will depend critically on leveraging understanding of the means by which antibodies with specific functional profiles could be elicited, which effector functions could provide optimal protection, and perhaps most critically, how to efficiently recruit the innate effector cells present at sites of infection.