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

Ann Hessell, J. Pablo Jaworski, Erin Epson, Kenta Matsuda, Shilpi Pandey, Christoph Kahl, Jason Reed, William F. Sutton, Katherine B. Hammond, Tracy A. Cheever, Philip T. Barnette, Alfred W. Legasse, Shannon Planer, Jeffrey Stanton, Amarendra Pegu, Xuejun Chen, Keyun Wang, Don Siess, David Burke, Byung ParkMichael Axthelm, Anne Lewis, Vanessa M. Hirsch, Barney S. Graham, John R. Mascola, Jonah Sacha, Nancy Haigwood

Research output: Contribution to journalArticle

88 Scopus citations

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 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 + T cell depletion. These results suggest that early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs.

Original languageEnglish (US)
Pages (from-to)362-368
Number of pages7
JournalNature Medicine
Volume22
Issue number4
DOIs
StatePublished - Apr 1 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Hessell, A., Jaworski, J. P., Epson, E., Matsuda, K., Pandey, S., Kahl, C., Reed, J., Sutton, W. F., Hammond, K. B., Cheever, T. A., Barnette, P. T., Legasse, A. W., Planer, S., Stanton, J., Pegu, A., Chen, X., Wang, K., Siess, D., Burke, D., ... Haigwood, N. (2016). Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques. Nature Medicine, 22(4), 362-368. https://doi.org/10.1038/nm.4063