Characterization of a vaccine-elicited human antibody with sequence homology to VRC01-class antibodies that binds the C1C2 gp120 domain
Year: 2022
Type: article
Abstract: 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.
Source: Science Advances
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
Awards: G640104970, G6680631498, G8671069964, G9000123548, HIV Vaccine Trials Network Laboratory Center, ALS Efficiently Networking Advanced Beam Line Experiments (ALS-ENABLE), Stem Cell and Transplantation Biology, Immune Responses to Malaria, HIV and SARS-CoV-2 Infection and Immunization, Consortium for HIV/AIDS Vaccine Development, Center for AIDS Research
OpenAlex ID: W4229020479