Opportunities to Exploit Non-Neutralizing HIV-Specific Antibody Activity
Margaret E. Ackerman and Galit Alter
Affiliation: Ragon Institute of MGH, MIT, and Harvard University Cambridge, MA 02139 USA
Keywords: ADCC, antibody, effector function, FcgR, HIV, IgG, passive transfer, phagocytosis, vaccine.
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.
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