Complementary antibody lineages achieve neutralization breadth in an HIV-1 infected elite neutralizer.

Autor: van Schooten J; Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, The Netherlands., Schorcht A; Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, The Netherlands., Farokhi E; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America., Umotoy JC; Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, The Netherlands., Gao H; Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America., van den Kerkhof TLGM; Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, The Netherlands.; Department of Experimental Immunology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, The Netherlands., Dorning J; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America., Rijkhold Meesters TG; Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, The Netherlands., van der Woude P; Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, The Netherlands., Burger JA; Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, The Netherlands., Bijl T; Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, The Netherlands., Ghalaiyini R; Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, The Netherlands., Torrents de la Peña A; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America., Turner HL; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America., Labranche CC; Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America., Stanfield RL; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America., Sok D; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, United States of America.; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America.; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, California, United States of America.; International AIDS Vaccine Initiative, New York, New York, United States of America., Schuitemaker H; Department of Experimental Immunology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, The Netherlands., Montefiori DC; Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America., Burton DR; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, United States of America.; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America.; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, California, United States of America.; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America., Ozorowski G; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America.; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, California, United States of America., Seaman MS; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America., Wilson IA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America.; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, California, United States of America.; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, United States of America., Sanders RW; Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, The Netherlands.; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York, United States of America., Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America.; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, California, United States of America., van Gils MJ; Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2022 Nov 17; Vol. 18 (11), pp. e1010945. Date of Electronic Publication: 2022 Nov 17 (Print Publication: 2022).
DOI: 10.1371/journal.ppat.1010945
Abstrakt: Broadly neutralizing antibodies (bNAbs) have remarkable breadth and potency against most HIV-1 subtypes and are able to prevent HIV-1 infection in animal models. However, bNAbs are extremely difficult to induce by vaccination. Defining the developmental pathways towards neutralization breadth can assist in the design of strategies to elicit protective bNAb responses by vaccination. Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. These results show that diverse NAbs can complement each other to achieve a broad and potent neutralizing serum response in HIV-1 infected individuals. Hence, the induction of combinations of moderately broad NAbs might be a viable vaccine strategy to protect against a wide range of circulating HIV-1 viruses.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2022 van Schooten et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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