Merck AIDS Vaccine Slows Progression to AIDS in Monkeys, Does Not Prevent Infection
Merck & Co. scientists announced yesterday at an AIDS conference in Keystone, Colo., that a common cold virus has proven to be an "effective vehicle to deliver a potent anti-AIDS vaccine to monkeys," the Philadelphia Inquirer reports. At a closed-door meeting on "AIDS Vaccines in the New Millenium," scientists announced that the vaccine, delivered in "disarmed" adenovirus, did not block HIV infection nor rid the body of infection, but suppressed the virus to levels "too low to be detected," allowing HIV-infected monkeys to remain healthy for more than a year (Collins, Philadelphia Inquirer, 4/2). Twenty-one monkeys were infected with an "especially nasty" combination of HIV and simian immunodeficiency virus, the monkey counterpart to HIV. The virus "quickly" manifested and generated 100 million virion copies per cubic centimeter of blood. Of the six control monkeys that were not given any vaccine, five developed AIDS-like illnesses and four have died, according to John Shriver, Merck's director of vaccine research. None of the monkeys given the adenovirus vaccine have developed any "AIDS-like" illnesses and the amount of virus in the bloodstream has been reduced to about 500 copies per cubic centimeter. Shriver warned that the studies are "very early," and that it is "impossible to predict" whether any of Merck's experimental vaccines will work in humans (Sternberg, USA Today, 4/2).
Using the Gag Gene
The vaccine is an improved version of one detailed by company scientists last year. Working with "relatively new" knowledge of the interaction between HIV and the human immune system, researchers became "convinced" that an effective vaccine "must" stimulate the release of CD8+ cells, or "killer T cells," specific immune cells that can "seek out" HIV-infected cells and "destroy" them, thereby "squelching the virus' ability to replicate and spread." Researchers learned that proteins produced by three of HIV's major genes stimulated a killer T cell response, but the gene known as gag was the most effective stimulator. Researchers first injected monkeys with the genes alone, an approach called "naked DNA," but the genes alone were not generating the "strong response" for which researchers had hoped. Last year, researchers "stitched" the genes into a deactivated adenovirus, which is unable to cause colds. Researchers hoped they could "harnes[s]" the adenovirus' "natural viral action" to deliver the DNA to immune cells in order to trigger the release of the killer T cells (Waldholz, Wall Street Journal, 4/2). Adenovirus was chosen because it typically invades dendritic cells, cells that play a "pivotal" role in immune response because they "pick up" invading viruses and "alert" other immune cells into response. They are found in all parts of the body, including mucosal cells in the vagina, making them "potentially very important" in fighting sexual transmission of HIV (Philadelphia Inquirer, 4/2). In all, researchers tested five vaccines, each containing the gag gene. In addition to the adenovirus vaccine, one vaccine used gag in vaccinia virus, the virus used in the original smallpox vaccine, and three vaccines used the naked DNA approach with or without booster shots of adjuvants. The naked DNA approach with a booster of an adjuvant called CRL-1005 produced an immune response "similar" to but "less dramatic" than the adenovirus vaccine.
'Good Stuff' Down the Road
"This [research] is the manifestation of what we in the field have been saying: We have good stuff in the pipeline," Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said. Two
other research groups -- one at Emory University and one at Harvard Medical School -- have achieved "similar" results, but the Merck project is the only one to use a "cell-mediated immunity" approach (Brown, Washington Post, 4/2). Merck's vaccine is still in the early stages and faces "at least" three years of safety trials before it can move into large-scale efficacy trials, which may take an additional three to five years to complete. Merck plans to continue testing the adenovirus vaccine and the naked DNA/adjuvant approach, as well as an approach that "prime[s]" the immune system with naked DNA before administering the adenovirus, which yielded the study's "best" results. Small human trials are being conducted in several U.S. medical centers to determine whether "double inoculation" is safe. The ultimate goal of HIV vaccine research is to block the virus from "ever taking hold," John Moore, a vaccine researcher at Weill Medical
College-Cornell University, said. But researchers have not determined how to produce an antibody response to "stimulate" the necessary combination of "neutralizing antibodies" and killer T cells (Wall Street Journal, 4/2). A vaccine that prevented infection would still "likely have a major effect on the spread of the virus" because epidemiological evidence shows that people with lower viral levels are "less likely" to transmit the virus (Philadelphia Inquirer, 4/2).
