Characterization of a vaccine-elicited human antibody with sequence homology to VRC01-class antibodies that binds the C1C2 gp120 domain

Author:

Gray Matthew D.1ORCID,Feng Junli1ORCID,Weidle Connor E.1ORCID,Cohen Kristen W.1ORCID,Ballweber-Fleming Lamar1ORCID,MacCamy Anna J.1ORCID,Huynh Crystal N.1,Trichka Josephine J.1ORCID,Montefiori David2,Ferrari Guido2ORCID,Pancera Marie13ORCID,McElrath M. Juliana145ORCID,Stamatatos Leonidas14ORCID

Affiliation:

1. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

2. Duke Human Vaccine Institute, Durham, NC 27710, USA.

3. Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD 20892, USA.

4. Department of Global Health, University of Washington, Seattle, WA 98195, USA.

5. Department of Medicine, University of Washington, Seattle, WA 98195, USA.

Abstract

Broadly HIV-1–neutralizing VRC01-class antibodies bind the CD4-binding site of Env and contain V H 1-2*02–derived heavy chains paired with light chains expressing five–amino acid–long CDRL3s. Their unmutated germline forms do not recognize HIV-1 Env, and their lack of elicitation in human clinical trials could be due to the absence of activation of the corresponding naïve B cells by the vaccine immunogens. To address this point, we examined Env-specific B cell receptor sequences from participants in the HVTN 100 clinical trial. Of all the sequences analyzed, only one displayed homology to VRC01-class antibodies, but the corresponding antibody (FH1) recognized the C1C2 gp120 domain. For FH1 to switch epitope recognition to the CD4-binding site, alterations in the CDRH3 and CDRL3 were necessary. Only germ line–targeting Env immunogens efficiently activated VRC01 B cells, even in the presence of FH1 B cells. Our findings support the use of these immunogens to activate VRC01 B cells in humans.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3