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Viruses 2015, 7(9), 5115-5132; doi:10.3390/v7092856

Conformational Masking and Receptor-Dependent Unmasking of Highly Conserved Env Epitopes Recognized by Non-Neutralizing Antibodies That Mediate Potent ADCC against HIV-1

1
Division of Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA
2
Centre de Recherche du CHUM, Department of Microbiology, Infectiology, and Immunology, Université de Montréal, Montreal, QC H2X 0A9, Canada
*
Author to whom correspondence should be addressed.
Academic Editor: Andrew Ward
Received: 3 June 2015 / Revised: 12 August 2015 / Accepted: 18 August 2015 / Published: 18 September 2015
(This article belongs to the Special Issue Viral Glycoprotein Structure)
View Full-Text   |   Download PDF [1024 KB, uploaded 18 September 2015]   |  

Abstract

The mechanism of antibody-mediated protection is a major focus of HIV-1 vaccine development and a significant issue in the control of viremia. Virus neutralization, Fc-mediated effector function, or both, are major mechanisms of antibody-mediated protection against HIV-1, although other mechanisms, such as virus aggregation, are known. The interplay between virus neutralization and Fc-mediated effector function in protection against HIV-1 is complex and only partially understood. Passive immunization studies using potent broadly neutralizing antibodies (bnAbs) show that both neutralization and Fc-mediated effector function provides the widest dynamic range of protection; however, a vaccine to elicit these responses remains elusive. By contrast, active immunization studies in both humans and non-human primates using HIV-1 vaccine candidates suggest that weakly neutralizing or non-neutralizing antibodies can protect by Fc-mediated effector function, albeit with a much lower dynamic range seen for passive immunization with bnAbs. HIV-1 has evolved mechanisms to evade each type of antibody-mediated protection that must be countered by a successful AIDS vaccine. Overcoming the hurdles required to elicit bnAbs has become a major focus of HIV-1 vaccine development. Here, we discuss a less studied problem, the structural basis of protection (and its evasion) by antibodies that protect only by potent Fc-mediated effector function. View Full-Text
Keywords: Fc; antibody; HIV-1; protection; effector-function; AIDS; vaccine Fc; antibody; HIV-1; protection; effector-function; AIDS; vaccine
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Lewis, G.K.; Finzi, A.; DeVico, A.L.; Pazgier, M. Conformational Masking and Receptor-Dependent Unmasking of Highly Conserved Env Epitopes Recognized by Non-Neutralizing Antibodies That Mediate Potent ADCC against HIV-1. Viruses 2015, 7, 5115-5132.

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