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Broadly Neutralizing Antibodies for HIV-1 Prevention

Given the absence of an effective vaccine for protection against HIV-1 infection, passive immunization strategies that utilize potent broadly neutralizing antibodies (bnAbs) to block acquisition of HIV-1 are being rigorously pursued in the clinical setting. bnAbs have demonstrated robust protection...

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Autores principales: Walsh, Stephen R., Seaman, Michael S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329589/
https://www.ncbi.nlm.nih.gov/pubmed/34354713
http://dx.doi.org/10.3389/fimmu.2021.712122
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author Walsh, Stephen R.
Seaman, Michael S.
author_facet Walsh, Stephen R.
Seaman, Michael S.
author_sort Walsh, Stephen R.
collection PubMed
description Given the absence of an effective vaccine for protection against HIV-1 infection, passive immunization strategies that utilize potent broadly neutralizing antibodies (bnAbs) to block acquisition of HIV-1 are being rigorously pursued in the clinical setting. bnAbs have demonstrated robust protection in preclinical animal models, and several leading bnAb candidates have shown favorable safety and pharmacokinetic profiles when tested individually or in combinations in early phase human clinical trials. Furthermore, passive administration of bnAbs in HIV-1 infected individuals has resulted in prolonged suppression of viral rebound following interruption of combination antiretroviral therapy, and robust antiviral activity when administered to viremic individuals. Recent results from the first efficacy trials testing repeated intravenous administrations of the anti-CD4 binding site bnAb VRC01 have demonstrated positive proof of concept that bnAb passive immunization can confer protection against HIV-1 infection in humans, but have also highlighted the considerable barriers that remain for such strategies to effectively contribute to control of the epidemic. In this review, we discuss the current status of clinical studies evaluating bnAbs for HIV-1 prevention, highlight lessons learned from the recent Antibody Mediated Prevention (AMP) efficacy trials, and provide an overview of strategies being employed to improve the breadth, potency, and durability of antiviral protection.
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spelling pubmed-83295892021-08-04 Broadly Neutralizing Antibodies for HIV-1 Prevention Walsh, Stephen R. Seaman, Michael S. Front Immunol Immunology Given the absence of an effective vaccine for protection against HIV-1 infection, passive immunization strategies that utilize potent broadly neutralizing antibodies (bnAbs) to block acquisition of HIV-1 are being rigorously pursued in the clinical setting. bnAbs have demonstrated robust protection in preclinical animal models, and several leading bnAb candidates have shown favorable safety and pharmacokinetic profiles when tested individually or in combinations in early phase human clinical trials. Furthermore, passive administration of bnAbs in HIV-1 infected individuals has resulted in prolonged suppression of viral rebound following interruption of combination antiretroviral therapy, and robust antiviral activity when administered to viremic individuals. Recent results from the first efficacy trials testing repeated intravenous administrations of the anti-CD4 binding site bnAb VRC01 have demonstrated positive proof of concept that bnAb passive immunization can confer protection against HIV-1 infection in humans, but have also highlighted the considerable barriers that remain for such strategies to effectively contribute to control of the epidemic. In this review, we discuss the current status of clinical studies evaluating bnAbs for HIV-1 prevention, highlight lessons learned from the recent Antibody Mediated Prevention (AMP) efficacy trials, and provide an overview of strategies being employed to improve the breadth, potency, and durability of antiviral protection. Frontiers Media S.A. 2021-07-20 /pmc/articles/PMC8329589/ /pubmed/34354713 http://dx.doi.org/10.3389/fimmu.2021.712122 Text en Copyright © 2021 Walsh and Seaman https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Walsh, Stephen R.
Seaman, Michael S.
Broadly Neutralizing Antibodies for HIV-1 Prevention
title Broadly Neutralizing Antibodies for HIV-1 Prevention
title_full Broadly Neutralizing Antibodies for HIV-1 Prevention
title_fullStr Broadly Neutralizing Antibodies for HIV-1 Prevention
title_full_unstemmed Broadly Neutralizing Antibodies for HIV-1 Prevention
title_short Broadly Neutralizing Antibodies for HIV-1 Prevention
title_sort broadly neutralizing antibodies for hiv-1 prevention
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329589/
https://www.ncbi.nlm.nih.gov/pubmed/34354713
http://dx.doi.org/10.3389/fimmu.2021.712122
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