Identification and characterization of a broadly cross-reactive HIV-1 human monoclonal antibody that binds to both gp120 and gp41.

Identification of broadly cross-reactive HIV-1-neutralizing antibodies (bnAbs) may assist vaccine immunogen design. Here we report a novel human monoclonal antibody (mAb), designated m43, which co-targets the gp120 and gp41 subunits of the HIV-1 envelope glycoprotein (Env). M43 bound to recombinant...

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Autores principales: Mei-Yun Zhang, Tingting Yuan, Jingjing Li, Andrew Rosa Borges, Jennifer D Watkins, Javier Guenaga, Zheng Yang, Yanping Wang, Richard Wilson, Yuxing Li, Victoria R Polonis, Seth H Pincus, Ruth M Ruprecht, Dimiter S Dimitrov
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spelling oai:doaj.org-article:0a713389e84f46b3a4b358d4a37ce0682021-11-18T07:06:11ZIdentification and characterization of a broadly cross-reactive HIV-1 human monoclonal antibody that binds to both gp120 and gp41.1932-620310.1371/journal.pone.0044241https://doaj.org/article/0a713389e84f46b3a4b358d4a37ce0682012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22970187/?tool=EBIhttps://doaj.org/toc/1932-6203Identification of broadly cross-reactive HIV-1-neutralizing antibodies (bnAbs) may assist vaccine immunogen design. Here we report a novel human monoclonal antibody (mAb), designated m43, which co-targets the gp120 and gp41 subunits of the HIV-1 envelope glycoprotein (Env). M43 bound to recombinant gp140 s from various primary isolates, to membrane-associated Envs on transfected cells and HIV-1 infected cells, as well as to recombinant gp120 s and gp41 fusion intermediate structures containing N-trimer structure, but did not bind to denatured recombinant gp140 s and the CD4 binding site (CD4bs) mutant, gp120 D368R, suggesting that the m43 epitope is conformational and overlaps the CD4bs on gp120 and the N-trimer structure on gp41. M43 neutralized 34% of the HIV-1 primary isolates from different clades and all the SHIVs tested in assays based on infection of peripheral blood mononuclear cells (PBMCs) by replication-competent virus, but was less potent in cell line-based pseudovirus assays. In contrast to CD4, m43 did not induce Env conformational changes upon binding leading to exposure of the coreceptor binding site, enhanced binding of mAbs 2F5 and 4E10 specific for the membrane proximal external region (MPER) of gp41 Envs, or increased gp120 shedding. The overall modest neutralization activity of m43 is likely due to the limited binding of m43 to functional Envs which could be increased by antibody engineering if needed. M43 may represent a new class of bnAbs targeting conformational epitopes overlapping structures on both gp120 and gp41. Its novel epitope and possibly new mechanism(s) of neutralization could helpdesign improved vaccine immunogens and candidate therapeutics.Mei-Yun ZhangTingting YuanJingjing LiAndrew Rosa BorgesJennifer D WatkinsJavier GuenagaZheng YangYanping WangRichard WilsonYuxing LiVictoria R PolonisSeth H PincusRuth M RuprechtDimiter S DimitrovPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e44241 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Mei-Yun Zhang
Tingting Yuan
Jingjing Li
Andrew Rosa Borges
Jennifer D Watkins
Javier Guenaga
Zheng Yang
Yanping Wang
Richard Wilson
Yuxing Li
Victoria R Polonis
Seth H Pincus
Ruth M Ruprecht
Dimiter S Dimitrov
Identification and characterization of a broadly cross-reactive HIV-1 human monoclonal antibody that binds to both gp120 and gp41.
description Identification of broadly cross-reactive HIV-1-neutralizing antibodies (bnAbs) may assist vaccine immunogen design. Here we report a novel human monoclonal antibody (mAb), designated m43, which co-targets the gp120 and gp41 subunits of the HIV-1 envelope glycoprotein (Env). M43 bound to recombinant gp140 s from various primary isolates, to membrane-associated Envs on transfected cells and HIV-1 infected cells, as well as to recombinant gp120 s and gp41 fusion intermediate structures containing N-trimer structure, but did not bind to denatured recombinant gp140 s and the CD4 binding site (CD4bs) mutant, gp120 D368R, suggesting that the m43 epitope is conformational and overlaps the CD4bs on gp120 and the N-trimer structure on gp41. M43 neutralized 34% of the HIV-1 primary isolates from different clades and all the SHIVs tested in assays based on infection of peripheral blood mononuclear cells (PBMCs) by replication-competent virus, but was less potent in cell line-based pseudovirus assays. In contrast to CD4, m43 did not induce Env conformational changes upon binding leading to exposure of the coreceptor binding site, enhanced binding of mAbs 2F5 and 4E10 specific for the membrane proximal external region (MPER) of gp41 Envs, or increased gp120 shedding. The overall modest neutralization activity of m43 is likely due to the limited binding of m43 to functional Envs which could be increased by antibody engineering if needed. M43 may represent a new class of bnAbs targeting conformational epitopes overlapping structures on both gp120 and gp41. Its novel epitope and possibly new mechanism(s) of neutralization could helpdesign improved vaccine immunogens and candidate therapeutics.
format article
author Mei-Yun Zhang
Tingting Yuan
Jingjing Li
Andrew Rosa Borges
Jennifer D Watkins
Javier Guenaga
Zheng Yang
Yanping Wang
Richard Wilson
Yuxing Li
Victoria R Polonis
Seth H Pincus
Ruth M Ruprecht
Dimiter S Dimitrov
author_facet Mei-Yun Zhang
Tingting Yuan
Jingjing Li
Andrew Rosa Borges
Jennifer D Watkins
Javier Guenaga
Zheng Yang
Yanping Wang
Richard Wilson
Yuxing Li
Victoria R Polonis
Seth H Pincus
Ruth M Ruprecht
Dimiter S Dimitrov
author_sort Mei-Yun Zhang
title Identification and characterization of a broadly cross-reactive HIV-1 human monoclonal antibody that binds to both gp120 and gp41.
title_short Identification and characterization of a broadly cross-reactive HIV-1 human monoclonal antibody that binds to both gp120 and gp41.
title_full Identification and characterization of a broadly cross-reactive HIV-1 human monoclonal antibody that binds to both gp120 and gp41.
title_fullStr Identification and characterization of a broadly cross-reactive HIV-1 human monoclonal antibody that binds to both gp120 and gp41.
title_full_unstemmed Identification and characterization of a broadly cross-reactive HIV-1 human monoclonal antibody that binds to both gp120 and gp41.
title_sort identification and characterization of a broadly cross-reactive hiv-1 human monoclonal antibody that binds to both gp120 and gp41.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/0a713389e84f46b3a4b358d4a37ce068
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