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Identification of a novel broadly HIV-1-neutralizing antibody from a CRF01_AE-infected Chinese donor

The isolation and characterization of monoclonal broadly neutralizing antibodies (nAbs) from natural HIV-1-infected individuals play very important roles in understanding nAb responses to HIV-1 infection and designing vaccines and therapeutics. Many broadly nAbs have been isolated from individuals i...

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Autores principales: Ju, Bin, Li, Dan, Ren, Li, Hou, Jiali, Hao, Yanling, Liang, Hua, Wang, Shuo, Zhu, Jiang, Wei, Min, Shao, Yiming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210191/
https://www.ncbi.nlm.nih.gov/pubmed/30382080
http://dx.doi.org/10.1038/s41426-018-0175-1
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author Ju, Bin
Li, Dan
Ren, Li
Hou, Jiali
Hao, Yanling
Liang, Hua
Wang, Shuo
Zhu, Jiang
Wei, Min
Shao, Yiming
author_facet Ju, Bin
Li, Dan
Ren, Li
Hou, Jiali
Hao, Yanling
Liang, Hua
Wang, Shuo
Zhu, Jiang
Wei, Min
Shao, Yiming
author_sort Ju, Bin
collection PubMed
description The isolation and characterization of monoclonal broadly neutralizing antibodies (nAbs) from natural HIV-1-infected individuals play very important roles in understanding nAb responses to HIV-1 infection and designing vaccines and therapeutics. Many broadly nAbs have been isolated from individuals infected with HIV-1 clade A, B, C, etc., but, as an important recombinant virus, the identification of broadly nAbs in CRF01_AE-infected individuals remains elusive. In this study, we used antigen-specific single B-cell sorting and monoclonal antibody expression to isolate monoclonal antibodies from a CRF01_AE-infected Chinese donor (GX2016EU04), a broad neutralizer based on neutralizing activity against a cross-clade virus panel. We identified a series of HIV-1 monoclonal cross-reactive nAbs, termed F2, H6, BF8, F4, F8, BE7, and F6. F6 could neutralize 21 of 37 tested HIV-1 Env-pseudotyped viruses (57%) with a geometric mean value of 12.15 μg/ml. Heavy and light chains of F6 were derived from IGHV4-34 and IGKV 2-28 germlines, complementarity determining region (CDR) 3 loops were composed of 18 and 9 amino acids, and somatic hypermutations (SHMs) were 16.14% and 11.83% divergent from their respective germline genes. F6 was a GP120-specific nAb and recognized the linear epitope. We identified for the first time a novel broadly HIV-1-neutralizing antibody, termed F6, from a CRF01_AE-infected donor, which could enrich the research of HIV-1 nAbs and provide useful insights for designing vaccine immunogens and antibody-based therapeutics.
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spelling pubmed-62101912018-11-02 Identification of a novel broadly HIV-1-neutralizing antibody from a CRF01_AE-infected Chinese donor Ju, Bin Li, Dan Ren, Li Hou, Jiali Hao, Yanling Liang, Hua Wang, Shuo Zhu, Jiang Wei, Min Shao, Yiming Emerg Microbes Infect Article The isolation and characterization of monoclonal broadly neutralizing antibodies (nAbs) from natural HIV-1-infected individuals play very important roles in understanding nAb responses to HIV-1 infection and designing vaccines and therapeutics. Many broadly nAbs have been isolated from individuals infected with HIV-1 clade A, B, C, etc., but, as an important recombinant virus, the identification of broadly nAbs in CRF01_AE-infected individuals remains elusive. In this study, we used antigen-specific single B-cell sorting and monoclonal antibody expression to isolate monoclonal antibodies from a CRF01_AE-infected Chinese donor (GX2016EU04), a broad neutralizer based on neutralizing activity against a cross-clade virus panel. We identified a series of HIV-1 monoclonal cross-reactive nAbs, termed F2, H6, BF8, F4, F8, BE7, and F6. F6 could neutralize 21 of 37 tested HIV-1 Env-pseudotyped viruses (57%) with a geometric mean value of 12.15 μg/ml. Heavy and light chains of F6 were derived from IGHV4-34 and IGKV 2-28 germlines, complementarity determining region (CDR) 3 loops were composed of 18 and 9 amino acids, and somatic hypermutations (SHMs) were 16.14% and 11.83% divergent from their respective germline genes. F6 was a GP120-specific nAb and recognized the linear epitope. We identified for the first time a novel broadly HIV-1-neutralizing antibody, termed F6, from a CRF01_AE-infected donor, which could enrich the research of HIV-1 nAbs and provide useful insights for designing vaccine immunogens and antibody-based therapeutics. Nature Publishing Group UK 2018-11-01 /pmc/articles/PMC6210191/ /pubmed/30382080 http://dx.doi.org/10.1038/s41426-018-0175-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ju, Bin
Li, Dan
Ren, Li
Hou, Jiali
Hao, Yanling
Liang, Hua
Wang, Shuo
Zhu, Jiang
Wei, Min
Shao, Yiming
Identification of a novel broadly HIV-1-neutralizing antibody from a CRF01_AE-infected Chinese donor
title Identification of a novel broadly HIV-1-neutralizing antibody from a CRF01_AE-infected Chinese donor
title_full Identification of a novel broadly HIV-1-neutralizing antibody from a CRF01_AE-infected Chinese donor
title_fullStr Identification of a novel broadly HIV-1-neutralizing antibody from a CRF01_AE-infected Chinese donor
title_full_unstemmed Identification of a novel broadly HIV-1-neutralizing antibody from a CRF01_AE-infected Chinese donor
title_short Identification of a novel broadly HIV-1-neutralizing antibody from a CRF01_AE-infected Chinese donor
title_sort identification of a novel broadly hiv-1-neutralizing antibody from a crf01_ae-infected chinese donor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210191/
https://www.ncbi.nlm.nih.gov/pubmed/30382080
http://dx.doi.org/10.1038/s41426-018-0175-1
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