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Prevention of virus transmission to macaque monkeys by a vaginally applied monoclonal antibody to HIV-1 gp120

Abstract

A topical microbicide reduces the probability of virus transmission when applied to the vagina or rectum of a person at risk of sexually acquiring HIV-1 infection1,2,3. An effective microbicide could significantly reduce the global spread of HIV-1, particularly if women were able to use it covertly to protect themselves. A microbicide could target the incoming virus and either permanently inactivate it or reduce its infectivity, or it could block receptors on susceptible cells near the sites of transmission1,2,3. We describe here how vaginal administration of the broadly neutralizing human monoclonal antibody b12 can protect macaques from simian-human immunodeficiency virus (SHIV) infection through the vagina. Only 3 of 12 animals receiving 5 mg b12 vaginally in either saline or a gel and then challenged vaginally (up to 2 h later) with SHIV-162P4 became infected. In contrast, infection occurred in 12 of 13 animals given various control agents under similar conditions. Lower amounts of b12 were less effective, suggesting that protection was dose dependent. These observations support the concept that viral entry inhibitors can help prevent the sexual transmission of HIV-1 to humans.

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Figure 1: Effect of vaginal b12 concentration on postinfection viral load in SHIV-162P4-challenged macaques.

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Acknowledgements

We thank C. Cheng-Mayer and J. Harouse (Aaron Diamond AIDS Research Center, New York) for the SHIV-162P4; R. Maguire and D. Phillips (The Population Council, New York) for the HMC; J. Mascola and M. Lewis for discussing their results from experiments of a similar design; L. Fresh, M. Mefford, A. Hessell, J. LeBlanc, S. Roscoe, R. Rodriguez and M. Paluch for technical assistance; and A. Ammann, M. Wainberg and R. Doms for advice and support. This work was funded by US National Institutes of Health grants AI52048, HD36310, AI49080, RR00164, AI33292, AI52057 and AI40877. M.P. is an Elizabeth Glaser Scientist, supported by the Elizabeth Glaser Pediatric AIDS Foundation. J.P.M. is a Stavros S. Niarchos Scholar. The Department of Microbiology and Immunology at the Weill Medical College gratefully acknowledges the support of the William Randolph Hearst Foundation.

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Correspondence to John P. Moore.

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D.B. has financial interests in the antibody b12 through The Scripps Research Institute. If the antibody were commercialized, he would receive some financial remuneration.

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Veazey, R., Shattock, R., Pope, M. et al. Prevention of virus transmission to macaque monkeys by a vaginally applied monoclonal antibody to HIV-1 gp120. Nat Med 9, 343–346 (2003). https://doi.org/10.1038/nm833

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