Recognition Patterns of the C1/C2 Epitopes Involved in Fc-Mediated Response in HIV-1 Natural Infection and the RV114 Vaccine Trial

ABSTRACT Antibodies (Abs) specific for CD4-induced envelope (Env) epitopes within constant region 1 and 2 (C1/C2) were induced in the RV144 vaccine trial, where antibody-dependent cellular cytotoxicity (ADCC) correlated with reduced risk of HIV-1 infection. We combined X-ray crystallography and fluo...

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Autores principales:	William D. Tolbert, Verna Van, Rebekah Sherburn, Marina Tuyishime, Fang Yan, Dung N. Nguyen, Sherry Stanfield-Oakley, David Easterhoff, Mattia Bonsignori, Barton F. Haynes, M. Anthony Moody, Krishanu Ray, Guido Ferrari, George K. Lewis, Marzena Pazgier
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	RV144 human immunodeficiency virus structural biology vaccines Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/dc7205bff9b2437a9295f2d6404618b1
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spelling	oai:doaj.org-article:dc7205bff9b2437a9295f2d6404618b12021-11-15T15:56:46ZRecognition Patterns of the C1/C2 Epitopes Involved in Fc-Mediated Response in HIV-1 Natural Infection and the RV114 Vaccine Trial10.1128/mBio.00208-202150-7511https://doaj.org/article/dc7205bff9b2437a9295f2d6404618b12020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00208-20https://doaj.org/toc/2150-7511ABSTRACT Antibodies (Abs) specific for CD4-induced envelope (Env) epitopes within constant region 1 and 2 (C1/C2) were induced in the RV144 vaccine trial, where antibody-dependent cellular cytotoxicity (ADCC) correlated with reduced risk of HIV-1 infection. We combined X-ray crystallography and fluorescence resonance energy transfer-fluorescence correlation spectroscopy to describe the molecular basis for epitopes of seven RV144 Abs and compared them to A32 and C11, C1/C2 Abs induced in HIV infection. Our data indicate that most vaccine Abs recognize the 7-stranded β-sandwich of gp120, a unique hybrid epitope bridging A32 and C11 binding sites. Although primarily directed at the 7-stranded β-sandwich, some accommodate the gp120 N terminus in C11-bound 8-stranded conformation and therefore recognize a broader range of CD4-triggered Env conformations. Our data also suggest that Abs of RV144 and RV305, the RV144 follow-up study, although likely initially induced by the ALVAC-HIV prime encoding full-length gp120, matured through boosting with truncated AIDSVAX gp120 variants. IMPORTANCE Antibody-dependent cellular cytotoxicity (ADCC) correlated with a reduced risk of infection from HIV-1 in the RV144 vaccine trial, the only HIV-1 vaccine trial to date to show any efficacy. Antibodies specific for CD4-induced envelope (Env) epitopes within constant region 1 and 2 (cluster A region) were induced in the RV144 trial and their ADCC activities were implicated in the vaccine efficacy. We present structural analyses of the antigen epitope targets of several RV144 antibodies specific for this region and C11, an antibody induced in natural infection, to show what the differences are in epitope specificities, mechanism of antigen recognition, and ADCC activities of antibodies induced by vaccination and during the course of HIV infection. Our data suggest that the truncated AIDSVAX gp120 variants used in the boost of the RV144 regimen may have shaped the vaccine response to this region, which could also have contributed to vaccine efficacy.William D. TolbertVerna VanRebekah SherburnMarina TuyishimeFang YanDung N. NguyenSherry Stanfield-OakleyDavid EasterhoffMattia BonsignoriBarton F. HaynesM. Anthony MoodyKrishanu RayGuido FerrariGeorge K. LewisMarzena PazgierAmerican Society for MicrobiologyarticleRV144human immunodeficiency virusstructural biologyvaccinesMicrobiologyQR1-502ENmBio, Vol 11, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	RV144 human immunodeficiency virus structural biology vaccines Microbiology QR1-502
spellingShingle	RV144 human immunodeficiency virus structural biology vaccines Microbiology QR1-502 William D. Tolbert Verna Van Rebekah Sherburn Marina Tuyishime Fang Yan Dung N. Nguyen Sherry Stanfield-Oakley David Easterhoff Mattia Bonsignori Barton F. Haynes M. Anthony Moody Krishanu Ray Guido Ferrari George K. Lewis Marzena Pazgier Recognition Patterns of the C1/C2 Epitopes Involved in Fc-Mediated Response in HIV-1 Natural Infection and the RV114 Vaccine Trial
description	ABSTRACT Antibodies (Abs) specific for CD4-induced envelope (Env) epitopes within constant region 1 and 2 (C1/C2) were induced in the RV144 vaccine trial, where antibody-dependent cellular cytotoxicity (ADCC) correlated with reduced risk of HIV-1 infection. We combined X-ray crystallography and fluorescence resonance energy transfer-fluorescence correlation spectroscopy to describe the molecular basis for epitopes of seven RV144 Abs and compared them to A32 and C11, C1/C2 Abs induced in HIV infection. Our data indicate that most vaccine Abs recognize the 7-stranded β-sandwich of gp120, a unique hybrid epitope bridging A32 and C11 binding sites. Although primarily directed at the 7-stranded β-sandwich, some accommodate the gp120 N terminus in C11-bound 8-stranded conformation and therefore recognize a broader range of CD4-triggered Env conformations. Our data also suggest that Abs of RV144 and RV305, the RV144 follow-up study, although likely initially induced by the ALVAC-HIV prime encoding full-length gp120, matured through boosting with truncated AIDSVAX gp120 variants. IMPORTANCE Antibody-dependent cellular cytotoxicity (ADCC) correlated with a reduced risk of infection from HIV-1 in the RV144 vaccine trial, the only HIV-1 vaccine trial to date to show any efficacy. Antibodies specific for CD4-induced envelope (Env) epitopes within constant region 1 and 2 (cluster A region) were induced in the RV144 trial and their ADCC activities were implicated in the vaccine efficacy. We present structural analyses of the antigen epitope targets of several RV144 antibodies specific for this region and C11, an antibody induced in natural infection, to show what the differences are in epitope specificities, mechanism of antigen recognition, and ADCC activities of antibodies induced by vaccination and during the course of HIV infection. Our data suggest that the truncated AIDSVAX gp120 variants used in the boost of the RV144 regimen may have shaped the vaccine response to this region, which could also have contributed to vaccine efficacy.
format	article
author	William D. Tolbert Verna Van Rebekah Sherburn Marina Tuyishime Fang Yan Dung N. Nguyen Sherry Stanfield-Oakley David Easterhoff Mattia Bonsignori Barton F. Haynes M. Anthony Moody Krishanu Ray Guido Ferrari George K. Lewis Marzena Pazgier
author_facet	William D. Tolbert Verna Van Rebekah Sherburn Marina Tuyishime Fang Yan Dung N. Nguyen Sherry Stanfield-Oakley David Easterhoff Mattia Bonsignori Barton F. Haynes M. Anthony Moody Krishanu Ray Guido Ferrari George K. Lewis Marzena Pazgier
author_sort	William D. Tolbert
title	Recognition Patterns of the C1/C2 Epitopes Involved in Fc-Mediated Response in HIV-1 Natural Infection and the RV114 Vaccine Trial
title_short	Recognition Patterns of the C1/C2 Epitopes Involved in Fc-Mediated Response in HIV-1 Natural Infection and the RV114 Vaccine Trial
title_full	Recognition Patterns of the C1/C2 Epitopes Involved in Fc-Mediated Response in HIV-1 Natural Infection and the RV114 Vaccine Trial
title_fullStr	Recognition Patterns of the C1/C2 Epitopes Involved in Fc-Mediated Response in HIV-1 Natural Infection and the RV114 Vaccine Trial
title_full_unstemmed	Recognition Patterns of the C1/C2 Epitopes Involved in Fc-Mediated Response in HIV-1 Natural Infection and the RV114 Vaccine Trial
title_sort	recognition patterns of the c1/c2 epitopes involved in fc-mediated response in hiv-1 natural infection and the rv114 vaccine trial
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/dc7205bff9b2437a9295f2d6404618b1
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Recognition Patterns of the C1/C2 Epitopes Involved in Fc-Mediated Response in HIV-1 Natural Infection and the RV114 Vaccine Trial

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