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Proc Natl Acad Sci U S A. 2014 Dec 9;111(49):17624-9. doi: 10.1073/pnas.1415789111. Epub 2014 Nov 24.

Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex.

Author information

1
Department of Immunology and Microbial Science, International AIDS Vaccine Initiative Neutralizing Antibody Center, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, International AIDS Vaccine Initiative, New York, NY 10038;
2
Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;
3
Department of Immunology and Microbial Science, International AIDS Vaccine Initiative Neutralizing Antibody Center, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery.
4
International AIDS Vaccine Initiative Neutralizing Antibody Center, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Department of Integrative Structural and Computational Biology, and Program in Molecular Structure and Function, The Hospital for Sick Children Research Institute and Departments of Biochemistry and Immunology, University of Toronto, Toronto, Ontario, M5G 0A4 Canada;
5
International AIDS Vaccine Initiative Neutralizing Antibody Center, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Department of Integrative Structural and Computational Biology, and.
6
Department of Integrative Structural and Computational Biology, and.
7
Beth Israel Deaconess Medical Center, Boston, MA 02215;
8
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021; and.
9
International AIDS Vaccine Initiative Neutralizing Antibody Center, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Department of Integrative Structural and Computational Biology, and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037;
10
Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021; and rws2002@med.cornell.edu burton@scripps.edu.
11
Department of Immunology and Microbial Science, International AIDS Vaccine Initiative Neutralizing Antibody Center, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, MA 02142 rws2002@med.cornell.edu burton@scripps.edu.

Abstract

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 µg/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.

KEYWORDS:

B cell; BG505 SOSIP; HIV; broadly neutralizing antibodies; vaccine

PMID:
25422458
PMCID:
PMC4267403
DOI:
10.1073/pnas.1415789111
[Indexed for MEDLINE]
Free PMC Article

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