Feb 13, 2003
A team headed by a Weill Cornell Medical College scientist has shown that a virus-inhibiting antibody applied vaginally as a topical microbicide can prevent SHIV infection in a monkey model. A National Institutes of Health (NIH)-funded study provides evidence that microbicides can prevent virus attachment and entry into the vagina and its associated tissues, a useful step in the development of an effective method to prevent the spread of HIV.
Published in the March issue of Nature Medicine, the study shows that monkeys treated with a monoclonal antibody microbicide, called b12, were significantly less likely to be infected with SHIV (an engineered simian-human version of human HIV) via the vaginal route than untreated monkeys exposed to the virus (25 percent versus 92 percent). Additionally, a greater dosage of b12, in gel or saline form, resulted in a greater ability to block infection.
Our findings are encouraging because several viral entry inhibitors are currently being developed as antiviral drugs. They should now be evaluated as microbicides to prevent infection, and not just as drugs to treat established infection, said Dr. John P. Moore, lead author of the article and Professor of Microbiology and Immunology at Weill Cornell Medical College. Our next step is to continue to evaluate several other entry inhibitors, to determine which are the most effective in the monkey model. An emphasis will be to identify compounds that are cheap enough to be used in the real world cheap, safe, and effective.
While production of the b12 antibody is presently prohibitively expensive, scientists affiliated with The Scripps Research Institute, and Epicyte Pharmaceutical, are developing an inexpensive way to produce the b12 antibody in plants, as a so-called plantibody. The b12 antibody recognizes the HIV-1 gp120 protein and prevents it from attaching to the CD4 receptor on human cells thereby preventing the fusion process by which infection occurs. Other microbicide candidates act in different ways by permanently inactivating the virus or otherwise reducing its infectivity. While the study examined the effect of microbicides on viral transmission via the vagina, rectal microbicides are also being developed. The scientific issues are similar, although not identical, said Dr. Moore, a scientist who has been studying the mechanism of HIV entry and its inhibition.
Dr. John Moore is also a member of the International AIDS Vaccine Initiative's (IAVI) Neutralizing Antibody Consortium (NAC), a team working on the development of a preventive AIDS vaccine.
There are 980,000 HIV-positive persons in the U.S.; one in five HIV-positive Americans is female. Globally, there are 42-million adults and children living with HIV/AIDS; 50 percent are women. The study was co-authored by Dr. Ronald S. Veazey, Dr. J. Christian Kirijan, and Dr. Preston A. Marx of the Tulane National Primate Research Center; Mr. Tom Ketas of Weill Cornell; Dr. Robin J. Shattock and Dr. Qinxue Hu of St. George's Hospital Medical School; Dr. Melissa Pope and Dr. Jennifer Jones of the Population Council; Dr. Per Johan Klasse of Wright-Fleming Institute; and Dr. Dennis R. Burton of The Scripps Research Institute.
The study was funded by a grant from the National Institute of Allergy and Infectious Diseases (NIAID). The Department of Microbiology and Immunology acknowledges the support of the William Randolph Hearst Foundation. Dr. John Moore is a Stavros S. Niarchos Foundation Scholar in the Program in Persistent Infections at Weill Cornell Medical College.