Antigen pressure from two founder viruses induces multiple insertions at a single antibody position to generate broadly neutralizing HIV antibodies.

Autor: Joyce C; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, United States of America.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, California, United States of America.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America., Murrell S; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America., Murrell B; Department of Medicine, University of California San Diego, San Diego, California, United States of America.; Department of Microbiology, Tumor and Cell biology, Karolinska Institutet, Stockholm, Sweden., Omorodion O; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, California, United States of America.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America.; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America., Ver LS; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America.; IAVI, New York, New York, United States of America., Carrico N; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America.; IAVI, New York, New York, United States of America., Bastidas R; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, United States of America.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, California, United States of America.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America., Nedellec R; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, United States of America.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, California, United States of America.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America., Bick M; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, United States of America.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, California, United States of America.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America., Woehl J; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America.; IAVI, New York, New York, United States of America., Zhao F; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, United States of America.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, California, United States of America.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America., Burns A; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America.; IAVI, New York, New York, United States of America., Barman S; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America.; IAVI, New York, New York, United States of America., Appel M; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America.; IAVI, New York, New York, United States of America., Ramos A; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America.; IAVI, New York, New York, United States of America., Wickramasinghe L; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America.; IAVI, New York, New York, United States of America., Eren K; Department of Medicine, University of California San Diego, San Diego, California, United States of America., Vollbrecht T; Department of Medicine, University of California San Diego, San Diego, California, United States of America.; Veterans Affairs San Diego Healthcare System, San Diego, California, United States of America., Smith DM; Department of Medicine, University of California San Diego, San Diego, California, United States of America., Kosakovsky Pond SL; Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, Pennsylvania, United States of America., McBride R; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, United States of America., Worth C; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, United States of America., Batista F; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, California, United States of America.; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America., Sok D; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, California, United States of America.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America.; IAVI, New York, New York, United States of America., Poignard P; Institut de Biologie Structurale, Université Grenoble Alpes, Commissariat à l'Energie Atomique, Centre National de Recherche Scientifique and Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France., Briney B; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, United States of America.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, California, United States of America.; Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, California, United States of America., Wilson IA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, California, United States of America.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America.; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.; Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, United States of America., Landais E; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, California, United States of America.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America.; IAVI, New York, New York, United States of America., Burton DR; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, United States of America.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, California, United States of America.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America.; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2023 Jun 29; Vol. 19 (6), pp. e1011416. Date of Electronic Publication: 2023 Jun 29 (Print Publication: 2023).
DOI: 10.1371/journal.ppat.1011416
Abstrakt: Vaccination strategies aimed at maturing broadly neutralizing antibodies (bnAbs) from naïve precursors are hindered by unusual features that characterize these Abs, including insertions and deletions (indels). Longitudinal studies of natural HIV infection cases shed light on the complex processes underlying bnAb development and have suggested a role for superinfection as a potential enhancer of neutralization breadth. Here we describe the development of a potent bnAb lineage that was elicited by two founder viruses to inform vaccine design. The V3-glycan targeting bnAb lineage (PC39-1) was isolated from subtype C-infected IAVI Protocol C elite neutralizer, donor PC39, and is defined by the presence of multiple independent insertions in CDRH1 that range from 1-11 amino acids in length. Memory B cell members of this lineage are predominantly atypical in phenotype yet also span the class-switched and antibody-secreting cell compartments. Development of neutralization breadth occurred concomitantly with extensive recombination between founder viruses before each virus separated into two distinct population "arms" that evolved independently to escape the PC39-1 lineage. Ab crystal structures show an extended CDRH1 that can help stabilize the CDRH3. Overall, these findings suggest that early exposure of the humoral system to multiple related Env molecules could promote the induction of bnAbs by focusing Ab responses to conserved epitopes.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Joyce 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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