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Cell. 2015 Jun 18;161(7):1505-15. doi: 10.1016/j.cell.2015.06.003.

Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice.

Author information

1
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
2
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
3
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
4
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
5
Department of Microbiology and Immunology, Weill Medical College, Cornell University, New York, NY 10065, USA.
6
Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
7
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute.
8
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
9
Howard Hughes Medical Institute; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
10
Department of Microbiology and Immunology, Weill Medical College, Cornell University, New York, NY 10065, USA; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
11
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Global Health, University of Washington, Seattle, WA 98109, USA.
12
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02129, USA. Electronic address: schief@scripps.edu.
13
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute. Electronic address: nussen@rockefeller.edu.

Abstract

A subset of individuals infected with HIV-1 develops broadly neutralizing antibodies (bNAbs) that can prevent infection, but it has not yet been possible to elicit these antibodies by immunization. To systematically explore how immunization might be tailored to produce them, we generated mice expressing the predicted germline or mature heavy chains of a potent bNAb to the CD4 binding site (CD4bs) on the HIV-1 envelope glycoprotein (Env). Immunogens specifically designed to activate B cells bearing germline antibodies are required to initiate immune responses, but they do not elicit bNAbs. In contrast, native-like Env trimers fail to activate B cells expressing germline antibodies but elicit bNAbs by selecting for a restricted group of light chains bearing specific somatic mutations that enhance neutralizing activity. The data suggest that vaccination to elicit anti-HIV-1 antibodies will require immunization with a succession of related immunogens.

PMID:
26091035
PMCID:
PMC4604566
DOI:
10.1016/j.cell.2015.06.003
[Indexed for MEDLINE]
Free PMC Article
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