Identification of IOMA-class neutralizing antibodies targeting the CD4-binding site on the HIV-1 envelope glycoprotein

Jelle Schooten, Elinaz Farokhi, Anna Schorcht, Tom L. G. M. Kerkhof, Hongmei Gao, Patricia Woude, Judith A. Burger, Tim G. Rijkhold Meesters, Tom Bijl, Riham Ghalaiyini, Hannah L. Turner, Jessica Dorning, Barbera D. C. Schaik, Antoine H. C. Kampen, Celia C. Labranche, Robyn L. Stanfield, Devin Sok, David C. Montefiori, Dennis R. Burton, Michael S. Seaman, Gabriel Ozorowski, Ian A. Wilson, Rogier W. Sanders, Andrew B. Ward and Marit J. Gils ()
Additional contact information
Jelle Schooten: University of Amsterdam
Elinaz Farokhi: The Scripps Research Institute
Anna Schorcht: University of Amsterdam
Tom L. G. M. Kerkhof: University of Amsterdam
Hongmei Gao: Duke University Medical Center
Patricia Woude: University of Amsterdam
Judith A. Burger: University of Amsterdam
Tim G. Rijkhold Meesters: University of Amsterdam
Tom Bijl: University of Amsterdam
Riham Ghalaiyini: University of Amsterdam
Hannah L. Turner: The Scripps Research Institute
Jessica Dorning: Harvard Medical School
Barbera D. C. Schaik: University of Amsterdam
Antoine H. C. Kampen: University of Amsterdam
Celia C. Labranche: Duke University Medical Center
Robyn L. Stanfield: The Scripps Research Institute
Devin Sok: The Scripps Research Institute
David C. Montefiori: Duke University Medical Center
Dennis R. Burton: The Scripps Research Institute
Michael S. Seaman: Harvard Medical School
Gabriel Ozorowski: The Scripps Research Institute
Ian A. Wilson: The Scripps Research Institute
Rogier W. Sanders: University of Amsterdam
Andrew B. Ward: The Scripps Research Institute
Marit J. Gils: University of Amsterdam

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract A major goal of current HIV-1 vaccine design efforts is to induce broadly neutralizing antibodies (bNAbs). The VH1-2-derived bNAb IOMA directed to the CD4-binding site of the HIV-1 envelope glycoprotein is of interest because, unlike the better-known VH1-2-derived VRC01-class bNAbs, it does not require a rare short light chain complementarity-determining region 3 (CDRL3). Here, we describe three IOMA-class NAbs, ACS101-103, with up to 37% breadth, that share many characteristics with IOMA, including an average-length CDRL3. Cryo-electron microscopy revealed that ACS101 shares interactions with those observed with other VH1-2 and VH1-46-class bNAbs, but exhibits a unique binding mode to residues in loop D. Analysis of longitudinal sequences from the patient suggests that a transmitter/founder-virus lacking the N276 glycan might have initiated the development of these NAbs. Together these data strengthen the rationale for germline-targeting vaccination strategies to induce IOMA-class bNAbs and provide a wealth of sequence and structural information to support such strategies.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32208-0

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DOI: 10.1038/s41467-022-32208-0

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