Article

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

Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
Nature (Impact Factor: 42.35). 10/2012; DOI: 10.1038/nature11604

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 infection1, 2. Previous work showed that antibodies exert selective pressure on the virus but escape variants emerge within a short period of time3, 4. However, these experiments were performed before the recent discovery of more potent anti-HIV-1 antibodies and their improvement by structure-based design5, 6, 7, 8, 9. 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 therapy10, 11, 12, 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.

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