Identification of $\mathrm{IOMA}$-class neutralizing antibodies targeting the $\mathrm{CD4}$-binding site on the $\mathrm{HIV}$-1 envelope glycoprotein

van Schooten, Jelle; Farokhi, Elinaz; Schorcht, Anna; van den Kerkhof, Tom L. G. M.; Gao, Hongmei; van der Woude, Patricia; Burger, Judith A.; Meesters, Tim Rijkhold; Bijl, Tom; Ghalaiyini, Riham; Turner, Hannah L.; Dorning, Jessica; van Schaik, Barbera D. C.; van Kampen, Antoine H. C.; Labranche, Celia C.; Stanfield, Robyn L.; Sok, Devin; Montefiori, David C.; Burton, Dennis R.; Seaman, Michael S.; Ozorowski, Gabriel; Wilson, Ian A.; Sanders, Rogier W.; Ward, Andrew B.; van Gils, Marit J.

doi:10.1038/s41467-022-32208-0

Title: Identification of $$\mathrm{IOMA}$$-class neutralizing antibodies targeting the $$\mathrm{CD4}$$-binding site on the $$\mathrm{HIV}$$-1 envelope glycoprotein

Journal Article · Wed Aug 03 00:00:00 EDT 2022 · Nature Communications

DOI:https://doi.org/10.1038/s41467-022-32208-0· OSTI ID:1903871

^[1];

^[2]; Schorcht, Anna ^[1]; van den Kerkhof, Tom L. G. M. ^[1]; Gao, Hongmei ^[3]; van der Woude, Patricia ^[1]; Burger, Judith A. ^[1];

^[1]; Bijl, Tom ^[1]; Ghalaiyini, Riham ^[1]; Turner, Hannah L. ^[2]; Dorning, Jessica ^[4]; van Schaik, Barbera D. C. ^[1]; van Kampen, Antoine H. C. ^[4];

^[3]; Stanfield, Robyn L. ^[2]; Sok, Devin ^[5];

^[3];

^[6]; Seaman, Michael S. ^[4] more »

University of Amsterdam (Netherlands)
The Scripps Research Institute, La Jolla, CA (United States)
Duke University, Durham, NC (United States). Medical Center
Harvard Medical School, Boston, MA (United States)
The Scripps Research Institute, La Jolla, CA (United States); International AIDS Vaccine Initiative, New York, NY (United States)
The Scripps Research Institute, La Jolla, CA (United States); International AIDS Vaccine Initiative, New York, NY (United States); Massachusetts Institute of Technology (MIT), Cambridge, MA (United States)
University of Amsterdam (Netherlands); Cornell University, Ithaca, NY (United States). Weill Medical College

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.

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Research Organization:: The Scripps Research Inst., La Jolla, CA (United States); Duke Univ., Durham, NC (United States). Medical Center

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH); HIV Vaccine Research and Design (HIVRAD); Bill and Melinda Gates Foundation; European Union’s Horizon 2020; Netherlands Organization for Scientific Research (NWO)

Grant/Contract Number:: AC02-05CH11231; AC02-76SF00515:P30 GM124169-01; OPP1132237; INV002022; OPP1146996; HHSN272201800004C; 681137

OSTI ID:: 1903871

Journal Information:: Nature Communications, Vol. 13, Issue 1; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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antibodies
cryoelectron microscopy
HIV infections
x-ray crystallography

Title: Identification of $$\mathrm{IOMA}$$-class neutralizing antibodies targeting the $$\mathrm{CD4}$$-binding site on the $$\mathrm{HIV}$$-1 envelope glycoprotein

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