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Nature. 2016 May 5;533(7601):105-109. doi: 10.1038/nature17677. Epub 2016 Apr 27.

A single injection of anti-HIV-1 antibodies protects against repeated SHIV challenges.

Author information

1
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA.
2
Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892 USA; Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA.
3
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA; Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA.
4
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 USA.
5
Laboratory of Experimental Immunology, Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany.
6
Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne, 50937 Cologne, Germany.
7
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
8
Howard Hughes Medical Institute, Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany.
#
Contributed equally

Abstract

Despite the success of potent anti-retroviral drugs in controlling human immunodeficiency virus type 1 (HIV-1) infection, little progress has been made in generating an effective HIV-1 vaccine. Although passive transfer of anti-HIV-1 broadly neutralizing antibodies can protect mice or macaques against a single high-dose challenge with HIV or simian/human (SIV/HIV) chimaeric viruses (SHIVs) respectively, the long-term efficacy of a passive antibody transfer approach for HIV-1 has not been examined. Here we show, on the basis of the relatively long-term protection conferred by hepatitis A immune globulin, the efficacy of a single injection (20 mg kg(-1)) of four anti-HIV-1-neutralizing monoclonal antibodies (VRC01, VRC01-LS, 3BNC117, and 10-1074 (refs 9 - 12)) in blocking repeated weekly low-dose virus challenges of the clade B SHIVAD8. Compared with control animals, which required two to six challenges (median = 3) for infection, a single broadly neutralizing antibody infusion prevented virus acquisition for up to 23 weekly challenges. This effect depended on antibody potency and half-life. The highest levels of plasma-neutralizing activity and, correspondingly, the longest protection were found in monkeys administered the more potent antibodies 3BNC117 and 10-1074 (median = 13 and 12.5 weeks, respectively). VRC01, which showed lower plasma-neutralizing activity, protected for a shorter time (median = 8 weeks). The introduction of a mutation that extends antibody half-life into the crystallizable fragment (Fc) domain of VRC01 increased median protection from 8 to 14.5 weeks. If administered to populations at high risk of HIV-1 transmission, such an immunoprophylaxis regimen could have a major impact on virus transmission.

PMID:
27120156
PMCID:
PMC5127204
DOI:
10.1038/nature17677
[Indexed for MEDLINE]
Free PMC Article

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