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Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques

Authors :
Hessell, Ann J.
Jaworski, J. Pablo
Epson, Erin
Matsuda, Kenta
Pandey, Shilpi
Kahl, Christoph
Reed, Jason
Sutton, William F.
Hammond, Katherine B.
Cheever, Tracy A.
Barnette, Philip T.
Legasse, Alfred W.
Planer, Shannon
Stanton, Jeffrey J.
Pegu, Amarendra
Chen, Xuejun
Wang, Keyun
Siess, Don
Burke, David
Park, Byung S.
Axthelm, Michael K.
Lewis, Anne
Hirsch, Vanessa M.
Graham, Barney S.
Mascola, John R.
Sacha, Jonah B.
Haigwood, Nancy L.
Source :
Nature Medicine. April 1, 2016, p362, 9 p.
Publication Year :
2016

Abstract

Prevention of mother-to-child transmission (MTCT) of HIV remains a major objective where antenatal care is not readily accessible. We tested HIV-1-specific human neutralizing monoclonal antibodies (NmAbs) as a post-exposure therapy in an infant macaque model for intrapartum MTCT. One-month-old rhesus macaques were inoculated orally with the simian-human immunodeficiency virus [SHIV.sub.SF162P3]. On days 1, 4, 7 and 10 after virus exposure, we injected animals subcutaneously with NmAbs and quantified systemic distribution of NmAbs in multiple tissues within 24 h after antibody administration. Replicating virus was found in multiple tissues by day 1 in animals that were not treated. All NmAb-treated macaques were free of virus in blood and tissues at 6 months after exposure. We detected no anti-SHIV T cell responses in blood or tissues at necropsy, and no virus emerged after [CD8.sup.+] T cell depletion. These results suggest that early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs.<br />Recent advances in the discovery of human HIV NmAbs that have high potency and breadth of coverage have rekindled an interest in their use as pre-exposure prophylaxis, as well as [...]

Details

Language :
English
ISSN :
10788956
Database :
Gale General OneFile
Journal :
Nature Medicine
Publication Type :
Academic Journal
Accession number :
edsgcl.451941083
Full Text :
https://doi.org/10.1038/nm.4063