National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI110657
United States
Citation
Journal: Nat Commun / Year: 2022 Title: Identification of IOMA-class neutralizing antibodies targeting the CD4-binding site on the HIV-1 envelope glycoprotein. Authors: Jelle van Schooten / Elinaz Farokhi / Anna Schorcht / Tom L G M van den Kerkhof / Hongmei Gao / Patricia van der Woude / Judith A Burger / Tim G Rijkhold Meesters / Tom Bijl / Riham ...Authors: Jelle van Schooten / Elinaz Farokhi / Anna Schorcht / Tom L G M van den Kerkhof / Hongmei Gao / Patricia van der Woude / Judith A Burger / Tim G Rijkhold Meesters / Tom Bijl / Riham Ghalaiyini / Hannah L Turner / Jessica Dorning / Barbera D C van Schaik / Antoine H C van 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 / Marit J van Gils / 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 ...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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