The first 24h: targeting the window of opportunity for antibody-mediated protection against HIV-1 transmission

Purpose of reviewI will review evidence that antibodies protect against HIV-1 transmission in a short window of opportunity, involving neutralization, Fc-mediated effector function, or both.Recent findingsThe last decade witnessed a dramatic progress in the understanding of antibody-mediated protection against HIV-1, including active and passive immunization studies in nonhuman primates; association between reduced infection risk and the specificities and function of antibodies in the RV144 clinical trial; identification of potent, broadly neutralizing antibodies; high-resolution structural studies of the HIV-1 envelope trimer; and an increasing appreciation that Fc-mediated effector function is critical to protection against transmission for neutralizing and nonneutralizing antibodies. Less information is known about how antibodies protect in situ, except that they must do in the first 24h after exposure. New evidence suggests that antibodies protect in an acute innate immune environment involving the NXLRX1 inflammasome and transforming growth factor beta (TGF-) that favors infection and rapid dissemination of CCR6(+)ROR(+) Th17 cells.SummaryThese recent findings set the stage for understanding how antibodies can prevent the transmission of HIV-1. In this context, antibodies must prevent infection in an innate immune environment that strongly favors transmission. This information is key for the development of a vaccine against HIV-1.