Therapeutic Efficacy of Potent Neutralizing HIV-1-Specific Monoclonal Antibodies in SHIV-Infected Rhesus Monkeys
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Author
Moldt, Brian
Klein, Florian
Oliveira, Thiago Y.
Shekhar, Karthik
Gupta, Sanjana
Smith, Kaitlin M.
Borducchi, Erica N.
Cabral, Crystal
Smith, Jeffrey Y.
Blackmore, Stephen
Sanisetty, Srisowmya
Perry, James R.
Beck, Matthew
Lewis, Mark G.
Rinaldi, William
Chakraborty, Arup K.
Poignard, Pascal
Nussenzweig, Michel C.
Burton, Dennis R.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/nature12744Metadata
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Barouch, D. H., J. B. Whitney, B. Moldt, F. Klein, T. Y. Oliveira, J. Liu, K. E. Stephenson, et al. 2014. “Therapeutic Efficacy of Potent Neutralizing HIV-1-Specific Monoclonal Antibodies in SHIV-Infected Rhesus Monkeys.” Nature 503 (7475): 224-228. doi:10.1038/nature12744. http://dx.doi.org/10.1038/nature12744.Abstract
HIV-1-specific monoclonal antibodies (mAbs) with extraordinary potency and breadth have recently been described. In humanized mice, combinations of mAbs have been shown to suppress viremia, but the therapeutic potential of these mAbs has not yet been evaluated in primates with an intact immune system. Here we show that administration of a cocktail of HIV-1-specific mAbs, as well as the single glycan-dependent mAb PGT121, resulted in a rapid and precipitous decline of plasma viremia to undetectable levels in rhesus monkeys chronically infected with the pathogenic virus SHIV-SF162P3. A single mAb infusion afforded up to a 3.1 log decline of plasma viral RNA in 7 days and also reduced proviral DNA in peripheral blood, gastrointestinal mucosa, and lymph nodes without the development of viral resistance. Moreover, following mAb administration, host Gag-specific T lymphocyte responses exhibited improved functionality. Virus rebounded in the majority of animals after a median of 56 days when serum mAb titers had declined to undetectable levels, although a subset of animals maintained long-term virologic control in the absence of further mAb infusions. These data demonstrate a profound therapeutic effect of potent neutralizing HIV-1-specific mAbs in SHIV-infected rhesus monkeys as well as an impact on host immune responses. Our findings strongly encourage the investigation of mAb therapy for HIV-1 in humans.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017780/pdf/Terms of Use
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