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Science 15 October 2004:
Vol. 306. no. 5695, pp. 485 - 487
DOI: 10.1126/science.1099288
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Reports

Prevention of Vaginal SHIV Transmission in Rhesus Macaques Through Inhibition of CCR5

Michael M. Lederman,1*{dagger} Ronald S. Veazey,2* Robin Offord,3* Donald E. Mosier,4 Jason Dufour,2 Megan Mefford,2 Michael Piatak, Jr.,5 Jeffrey D. Lifson,5 Janelle R. Salkowitz,1 Benigno Rodriguez,1 Andrew Blauvelt,6{ddagger} Oliver Hartley3

Topical agents, such as microbicides, that can protect against human immunodeficiency virus (HIV) transmission are urgently needed. Using a chimeric simian/human immunodeficiency virus (SHIV SF162), which is tropic for the chemokine receptor CCR5, we report that topical application of high doses of PSC-RANTES, an amino terminus–modified analog of the chemokine RANTES, provided potent protection against vaginal challenge in rhesus macaques. These experimental findings have potentially important implications for understanding vaginal transmission of HIV and the design of strategies for its prevention.

1 Department of Medicine, Case Western Reserve University, University Hospitals, 2061 Cornell Road, Cleveland, OH 44106, USA.
2 Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433, USA.
3 Department of Structural Biology and Bioinformatics, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland.
4 Scripps Research Institute, 10550 Torrey Pines Road, La Jolla, CA 92037, USA.
5 AIDS Vaccine Program, SAIC Frederick, Inc., National Cancer Institute, Frederick, MD 21702-1201, USA.
6 Dermatology Branch, National Cancer Institute, Bethesda, MD 20892–1908, USA.



* These authors contributed equally to this work.

{ddagger} Present address: Department of Dermatology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.

{dagger} To whom correspondence should be addressed. E-mail: MXL6{at}case.edu

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