학술논문
HIV therapy by a combination of broadly neutralizing antibodies in humanized mice.
Document Type
Article
Author
Klein, Florian; Halper-Stromberg, Ariel; Horwitz, Joshua A.; Gruell, Henning; Scheid, Johannes F.; Bournazos, Stylianos; Mouquet, Hugo; Spatz, Linda A.; Diskin, Ron; Abadir, Alexander; Zang, Trinity; Dorner, Marcus; Billerbeck, Eva; Labitt, Rachael N.; Gaebler, Christian; Marcovecchio, Paola M.; Incesu, Reha-Baris; Eisenreich, Thomas R.; Bieniasz, Paul D.; Seaman, Michael S.
Source
Subject
*THERAPEUTICS
*HIV antibodies
*LABORATORY mice
*ANIMAL models in research
*HIV infections
*VIRAL load
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Language
ISSN
0028-0836
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. [ABSTRACT FROM AUTHOR]