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

AMA Style

Lewis GK, Finzi A, DeVico AL, 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(9):5115-5132. https://doi.org/10.3390/v7092856

Chicago/Turabian Style

Lewis, George K.; Finzi, Andrés; DeVico, Anthony L.; Pazgier, Marzena. 2015. "Conformational Masking and Receptor-Dependent Unmasking of Highly Conserved Env Epitopes Recognized by Non-Neutralizing Antibodies That Mediate Potent ADCC against HIV-1" Viruses 7, no. 9: 5115-5132. https://doi.org/10.3390/v7092856

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