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Nature. 2012 Dec 6;492(7427):118-22. doi: 10.1038/nature11604. Epub 2012 Oct 24.

HIV therapy by a combination of broadly neutralizing antibodies in humanized mice.

Author information

1
Laboratory of Molecular Immunology, The Rockefeller University; New York, New York 10065; United States.
2
Medizinische Fakultät, Westfälische Wilhelms-Universität Münster; D-48149 Münster; Germany.
3
Charite Universitätsmedizin; D-10117 Berlin; Germany.
4
Laboratory of Molecular Genetics and Immunology, The Rockefeller University; New York, New York 10065; United States.
5
Department of Microbiology and Immunology, Sophie Davis School of Biomedical Education, The City College of New York; New York, New York 10031; United States.
6
Division of Biology, California Institute of Technology; Pasadena, CA 91125; United States.
7
Aaron Diamond AIDS Research Center, Laboratory of Retrovirology, The Rockefeller University; New York, New York 10065; United States.
8
Laboratory of Virology and Infectious Diseases, The Rockefeller University; New York, New York 10065; United States.
9
Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden; D-01307 Dresden; Germany.
10
Howard Hughes Medical Institute.
11
Beth Israel Deaconess Med. Ctr.; Boston, MA 02215; United States.
#
Contributed equally

Abstract

Human antibodies to human immunodeficiency virus-1 (HIV-1) can neutralize a broad range of viral isolates in vitro and protect non-human primates against infection. Previous work showed that antibodies exert selective pressure on the virus but escape variants emerge within a short period of time. However, these experiments were performed before the recent discovery of more potent anti-HIV-1 antibodies and their improvement by structure-based design. Here we re-examine passive antibody transfer as a therapeutic modality in HIV-1-infected humanized mice. Although HIV-1 can escape from antibody monotherapy, combinations of broadly neutralizing antibodies can effectively control HIV-1 infection and suppress viral load to levels below detection. Moreover, in contrast to antiretroviral therapy, the longer half-life of antibodies led to control of viraemia for an average of 60 days after cessation of therapy. Thus, combinations of potent monoclonal antibodies can effectively control HIV-1 replication in humanized mice, and should be re-examined as a therapeutic modality in HIV-1-infected individuals.

PMID:
23103874
PMCID:
PMC3809838
DOI:
10.1038/nature11604
[Indexed for MEDLINE]
Free PMC Article

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