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

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 expression vectors. 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.