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

Lewis, George K.

Current Opinion in HIV and AIDS: November 2016 - Volume 11 - Issue 6 - p 561–568
doi: 10.1097/COH.0000000000000319
HIV VACCINE: Edited by Stephen J. Kent and Jerome H. Kim
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Purpose of review I 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 findings The 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 24 h after exposure. New evidence suggests that antibodies protect in an acute innate immune environment involving the NXLRX1 inflammasome and transforming growth factor beta (TGF-β) that favors infection and rapid dissemination of CCR6+RORγ+ Th17 cells.

Summary These 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.

Division of Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland, USA

Correspondence to George K. Lewis, PhD, Division of Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA. Tel: +1 443 540 0393; e-mail: glewis@ihv.umaryland.edu

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