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J Exp Med. 2014 Sep 22;211(10):2061-74. doi: 10.1084/jem.20132494. Epub 2014 Aug 25.

Passive transfer of modest titers of potent and broadly neutralizing anti-HIV monoclonal antibodies block SHIV infection in macaques.

Author information

1
Laboratory of Molecular Microbiology, Virology Laboratory, Vaccine Research Center, and Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
2
Department of Surgery, Duke University Medical Center, Durham, NC 27710.
3
Department of Immunology and Microbial Science, IAVI Neutralizing Antibody Center, and Center for HIV/AIDS Vaccine immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037 Department of Immunology and Microbial Science, IAVI Neutralizing Antibody Center, and Center for HIV/AIDS Vaccine immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037 Department of Immunology and Microbial Science, IAVI Neutralizing Antibody Center, and Center for HIV/AIDS Vaccine immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037.
4
Department of Structural Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
5
Division of Biology, California Institute of Technology, Pasadena, CA 91125 Howard Hughes Medical Institute, Chevy Chase, MD 20815.
6
Diagnostic and Research Services Branch, Office of the Director, National Institutes of Health, Bethesda, MD 20892.
7
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
8
Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, 75724 Paris, France.
9
Department of Immunology and Microbial Science, IAVI Neutralizing Antibody Center, and Center for HIV/AIDS Vaccine immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037 Department of Immunology and Microbial Science, IAVI Neutralizing Antibody Center, and Center for HIV/AIDS Vaccine immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037 Department of Immunology and Microbial Science, IAVI Neutralizing Antibody Center, and Center for HIV/AIDS Vaccine immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037 Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Boston, MA 021142.
10
Howard Hughes Medical Institute, Chevy Chase, MD 20815 Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.
11
Laboratory of Molecular Microbiology, Virology Laboratory, Vaccine Research Center, and Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 malm@nih.gov ynishimura@niaid.nih.gov.

Abstract

It is widely appreciated that effective human vaccines directed against viral pathogens elicit neutralizing antibodies (NAbs). The passive transfer of anti-HIV-1 NAbs conferring sterilizing immunity to macaques has been used to determine the plasma neutralization titers, which must be present at the time of exposure, to prevent acquisition of SIV/HIV chimeric virus (SHIV) infections. We administered five recently isolated potent and broadly acting anti-HIV neutralizing monoclonal antibodies (mAbs) to rhesus macaques and challenged them intrarectally 24 h later with either of two different R5-tropic SHIVs. By combining the results obtained from 60 challenged animals, we determined that the protective neutralization titer in plasma preventing virus infection in 50% of the exposed monkeys was relatively modest (∼1:100) and potentially achievable by vaccination.

PMID:
25155019
PMCID:
PMC4172223
DOI:
10.1084/jem.20132494
[Indexed for MEDLINE]
Free PMC Article

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