Identification of a CD4-binding site-directed antibody with ADCC activity from a chronic HIV-1B'-infected Chinese donor

Author:

Hu, Yuanyuan

Li, Dan

Fu, Hongyang

Hao, Yanling

Ren, Li

Wang, Shuo

Hu,Xintao

Shao, Yiming

Hong, Kunxue

Wang, Zheng
Author Address

State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Changping District, Beijing 102206, China.; Division of Research of Virology and Immunology, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Changping District, Beijing 102206, China., Present address: Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA., State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Changping District, Beijing 102206, China.; Division of Research of Virology and Immunology, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Changping District, Beijing 102206, China.. Electronic address: wangzheng@chinaaids.cn.,

Abstract:

Antibody-dependent cell-mediated cytotoxicity (ADCC) plays an important role in controlling HIV-1 invasion and replication in vivo. Isolation and identification of monoclonal antibodies (mAbs) with ADCC activity help design effective vaccines and develop novel treatment strategies. In this study, we first identified a broad neutralizer who had been infected with an HIV-1B' strain for over 10 years. Next, through probe-specific single-B-cell sorting and PCR amplification, we obtained genes for variable regions of the heavy chain (VHs) and light chain (VLs) of six antibodies and ligated them into an expression vector. After antibody expression and ELISA screening, we obtained a CD4-binding site-directed antibody (451-B4), whose VH and VL originated from the IGHV1-24 and IGLV1-40 germlines, respectively. Although 451-B4 neutralized only the SF162 tier 1 pseudovirus and 398F1 tier 2 pseudovirus, it could mediate comparable ADCC activity to a broadly neutralizing antibody, VRC01. The 451-B4 antibody will be a useful candidate for developing an ADCC-based treatment strategy against HIV-1 replication or latent infection in vivo. Copyright © 2021. Published by Elsevier B.V.

See More

Author Address