Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 49, Pages 17624-17629Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1415789111
Keywords
HIV; broadly neutralizing antibodies; BG505 SOSIP; B cell; vaccine
Categories
Funding
- International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Consortium [SFP1849]
- National Institutes of Health (NIH) [R01 AI033292, R01 AI84817, R37 AI36082]
- Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery Grant [UM1AI100663]
- HIV Vaccine Research and Design Program [P01 AI82362]
- NIH Interdisciplinary Training Program in Immunology [5T32AI007606-10]
- Dutch Aids Fonds [2012041, 2009012, 2011032]
- European Molecular Biology Organization Application Short-Term Fellowship [260-2013]
- Netherlands Organization for Scientific Research
- European Research Council [ERC-StG-2011-280829-SHEV]
- Canadian Institutes of Health Research fellowship
- Bill and Melinda Gates Foundation [38619]
- Ministry of Foreign Affairs of Denmark
- Irish Aid
- Ministry of Finance of Japan
- Ministry of Foreign Affairs of the Netherlands
- Norwegian Agency for Development Cooperation
- United Kingdom Department for International Development
- US Agency for International Development (USAID)
- American people through USAID
- Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery
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Broadly neutralizing antibodies (bnAbs) targeting the trimer apex of HIV envelope are favored candidates for vaccine design and immunotherapy because of their great neutralization breadth and potency. However, methods of isolating bnAbs against this site have been limited by the quaternary nature of the epitope region. Here we report the use of a recombinant HIV envelope trimer, BG505 SOSIP.664 gp140, as an affinity reagent to isolate quaternary-dependent bnAbs from the peripheral blood mononuclear cells of a chronically infected donor. The newly isolated bnAbs, named PGDM1400-1412, show a wide range of neutralization breadth and potency. One of these variants, PGDM1400, is exceptionally broad and potent with cross-clade neutralization coverage of 83% at a median IC50 of 0.003 mu g/mL. Overall, our results highlight the utility of BG505 SOSIP. 664 gp140 as a tool for the isolation of quaternary-dependent antibodies and reveal a mosaic of antibody responses against the trimer apex within a clonal family.
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