Immunization of cows with HIV envelope trimers generates broadly neutralizing antibodies to the V2-apex from the ultralong CDRH3 repertoire.

Autor: Altman PX; 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., Ozorowski G; 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., Stanfield RL; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America., Haakenson J; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, United States of America.; Applied Biomedical Science Institute, San Diego, California, United States of America., Appel M; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America.; International AIDS Vaccine Initiative, New York, New York, United States of America., Parren M; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, United States of America., Lee WH; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America., Sang H; Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medical, Kansas State University, Manhattan, Kansas, United States of America., Woehl J; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America.; International AIDS Vaccine Initiative, New York, New York, United States of America., Saye-Francisco K; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, United States of America., Sewall LM; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America., 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., Song G; 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., Porter K; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, United States of America., Landais E; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America.; International AIDS Vaccine Initiative, New York, New York, United States of America., Andrabi 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.; Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 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., Ward AB; 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., Mwangi W; Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medical, Kansas State University, Manhattan, Kansas, United States of America., Smider VV; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, United States of America.; Applied Biomedical Science Institute, San Diego, California, 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 Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, 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.; International AIDS Vaccine Initiative, New York, New York, United States of America.; Global Health Investment Corporation, New York, New York, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 Sep 09; Vol. 20 (9), pp. e1012042. Date of Electronic Publication: 2024 Sep 09 (Print Publication: 2024).
DOI: 10.1371/journal.ppat.1012042
Abstrakt: The generation of broadly neutralizing antibodies (bnAbs) to conserved epitopes on HIV Envelope (Env) is one of the cornerstones of HIV vaccine research. The animal models commonly used for HIV do not reliably produce a potent broadly neutralizing serum antibody response, with the exception of cows. Cows have previously produced a CD4 binding site response by homologous prime and boosting with a native-like Env trimer. In small animal models, other engineered immunogens were shown to focus antibody responses to the bnAb V2-apex region of Env. Here, we immunized two groups of cows (n = 4) with two regimens of V2-apex focusing Env immunogens to investigate whether antibody responses could be generated to the V2-apex on Env. Group 1 was immunized with chimpanzee simian immunodeficiency virus (SIV)-Env trimer that shares its V2-apex with HIV, followed by immunization with C108, a V2-apex focusing immunogen, and finally boosted with a cross-clade native-like trimer cocktail. Group 2 was immunized with HIV C108 Env trimer followed by the same HIV trimer cocktail as Group 1. Longitudinal serum analysis showed that one cow in each group developed serum neutralizing antibody responses to the V2-apex. Eight and 11 bnAbs were isolated from Group 1 and Group 2 cows, respectively, and showed moderate breadth and potency. Potent and broad responses in this study developed much later than previous cow immunizations that elicited CD4bs bnAbs responses and required several different immunogens. All isolated bnAbs were derived from the ultralong CDRH3 repertoire. The finding that cow antibodies can target more than one broadly neutralizing epitope on the HIV surface reveals the generality of elongated structures for the recognition of highly glycosylated proteins. The exclusive isolation of ultralong CDRH3 bnAbs, despite only comprising a small percent of the cow repertoire, suggests these antibodies outcompete the long and short CDRH3 antibodies during the bnAb response.
Competing Interests: VVS is a founder and owns equity in Taurus Biosciences LLC, San Diego, CA. The authors declare no other competing interests.
(Copyright: © 2024 Altman 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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