NEW YORK (Reuters Health) - Vaginal application of a highly concentrated solution containing the experimental antiviral PSC-RANTES protects female rhesus macaques from intravaginal exposure to simian HIV (SHIV) by preventing the virus from latching on to the CD4 cell surface receptor CCR5, which mediates HIV entry, according to a new study.
PSC-RANTES is a chemically synthesized version of the naturally occurring immune system chemokine RANTES, which has well-known antiviral properties.
In experiments described in the October 15th issue of the journal Science, scientists treated 30 female rhesus monkeys with progesterone to facilitate SHIV infection, applied varying concentrations of PSC-RANTES or placebo to the vaginas of the animals, and then exposed them to a virulent strain of SHIV.
Dr. Michael M. Lederman, a clinical immunologist from Case Western Reserve University in Cleveland, Ohio and colleagues report that topical application of PSC-RANTES provided “potent protection” against vaginal challenge with SHIV without detectable toxicity or histological changes.
At the highest dose - 4 milliliters of a one-millimolar concentration - PSC-RANTES protected all 5 monkeys from SHIV infection. The second highest dose (330 micromolar) protected 4 out of 5 monkeys treated and the third strongest concentration (100 micromolar) protected 3 of 5 animals.
“Because the vast majority of HIV infections are acquired via transmission across mucosal surfaces, strategies to prevent mucosal transmission are urgently needed,” the authors note. The current study suggests that it “seems reasonable” to pursue a strategy to prevent sexual HIV transmission that targets CCR5, they write.
Science editorial writer Jon Cohen notes that while microbicides have long had a “stepchild status” among AIDS researchers, nonprofits and governments have poured “substantial money” into microbicide research and development over the past several years, “bringing forward several cutting-edge concepts.”
Source: Science 2004;306:387,485-487. [ Google search on this article ]
MeSH Headings:Biological Factors: Chemotactic Factors: Immunologic and Biological Factors: Immunologic Factors: Membrane Proteins: Receptors, Cell Surface: Receptors, Immunologic: Receptors, Virus: Receptors, HIV: Receptors, Cytokine: Chemokines: RANTES: Receptors, Chemokine: Receptors, CCR5: Chemical Actions and Uses: Chemical Actions: Chemicals and DrugsCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
