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

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

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Veröffentlicht in:Science advances 2022-05, Vol.8 (18), p.eabm3948
Hauptverfasser: Gray, Matthew D, Feng, Junli, Weidle, Connor E, Cohen, Kristen W, Ballweber-Fleming, Lamar, MacCamy, Anna J, Huynh, Crystal N, Trichka, Josephine J, Montefiori, David, Ferrari, Guido, Pancera, Marie, McElrath, M Juliana, Stamatatos, Leonidas
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Sprache:eng
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Zusammenfassung:Broadly HIV-1-neutralizing VRC01-class antibodies bind the CD4-binding site of Env and contain V 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.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.abm3948