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

Autor: van Schooten J; Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, 1105AZ, The Netherlands., Farokhi E; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA., Schorcht A; Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, 1105AZ, The Netherlands., van den Kerkhof TLGM; Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, 1105AZ, The Netherlands., Gao H; Department of Surgery, Duke University Medical Center, Durham, NC, 27710, USA., van der Woude P; Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, 1105AZ, The Netherlands., Burger JA; Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, 1105AZ, The Netherlands., Meesters TGR; Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, 1105AZ, The Netherlands., Bijl T; Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, 1105AZ, The Netherlands., Ghalaiyini R; Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, 1105AZ, The Netherlands., Turner HL; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA., Dorning J; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA., van Schaik BDC; Bioinformatics Laboratory, Department of Epidemiology and Data Science, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, 1105AZ, The Netherlands., van Kampen AHC; Bioinformatics Laboratory, Department of Epidemiology and Data Science, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, 1105AZ, The Netherlands., Labranche CC; Department of Surgery, Duke University Medical Center, Durham, NC, 27710, USA., Stanfield RL; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA., Sok D; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA.; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA, 92037, USA.; International AIDS Vaccine Initiative, New York, NY, 10004, USA., Montefiori DC; Department of Surgery, Duke University Medical Center, Durham, NC, 27710, USA., Burton DR; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA.; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.; International AIDS Vaccine Initiative, New York, NY, 10004, USA.; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA., Seaman MS; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA., Ozorowski G; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA, 92037, USA., Wilson IA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA, 92037, USA.; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA., Sanders RW; Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, 1105AZ, The Netherlands.; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, 10065, USA., Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA, 92037, USA., van Gils MJ; Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, 1105AZ, The Netherlands. M.J.vangils@amsterdamumc.nl.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Aug 03; Vol. 13 (1), pp. 4515. Date of Electronic Publication: 2022 Aug 03.
DOI: 10.1038/s41467-022-32208-0
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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