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

Journal Article (Journal Article)

Broadly HIV-1-neutralizing VRC01-class antibodies bind the CD4-binding site of Env and contain VH 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.

Full Text

Duke Authors

Cited Authors

  • Gray, MD; Feng, J; Weidle, CE; Cohen, KW; Ballweber-Fleming, L; MacCamy, AJ; Huynh, CN; Trichka, JJ; Montefiori, D; Ferrari, G; Pancera, M; McElrath, MJ; Stamatatos, L

Published Date

  • May 2022

Published In

Volume / Issue

  • 8 / 18

Start / End Page

  • eabm3948 -

PubMed ID

  • 35507661

Pubmed Central ID

  • PMC9067929

Electronic International Standard Serial Number (EISSN)

  • 2375-2548

International Standard Serial Number (ISSN)

  • 2375-2548

Digital Object Identifier (DOI)

  • 10.1126/sciadv.abm3948

Language

  • eng