The encouraging results from laboratory tests do not yet prove the vaccines will work in people. "The only way to establish protection is to do a phase 3 trial," notes Carole A. Heilman, associate director of the division of AIDS at the National Institutes of Health. But the latest finding show that the new candidates have potential. "There seems to be more activity going on in AIDS vaccines in general," Heilman comments.

David B. Weiner the University of Pennsylvania recently announced another encouraging discovery. He and his colleagues were able to make two chimpanzees resistant to HIV infection (like humans, chimps are susceptible to the virus) by vaccinating them with a preparation based on "naked" DNA encoding HIV genes. Conventional vaccines employ killed or modified pathogens, or proteins made by them, rather than DNA. In contrast, a DNA vaccine like the one used by Weiner works by allowing the body's cells to make viral proteins in a harmless, non-infectious form; the immune system then gets sensitized to them, which helps prevent subsequent infection by the actual virus. Weiner's result provides evidence that a naked DNA vaccine might work in people, although there are substantial differences between chimpanzees and humans: most notably, chimps usually do not become sick with AIDS when infected with HIV.

Scientists have also learned a lot in recent years about the molecular-level interactions between HIV and the receptors on cells of the body, which provide the virus with its foothold for entering the cells. "We can work to find the best immunogens," Heilman declares. Moreover, researchers have acquired new tools in the form of genetically-engineered small animals, such as rabbits, that are susceptible to infection with HIV. (Non-primates are normally immune to infection with HIV and its close viral relatives.) These animals will speed the testing of anti-AIDS therapies and vaccines.

Plans are moving ahead to test various types of HIV vaccine in humans in intermediate and large-scale trials; studies are now being planned in Uganda, Thailand and the U.S. And despite the past gloom in the field, Heilman says there is no reason to believe that President Clinton's goal is out of reach. Most successful vaccines are the end result of trail and error modifications, she notes. But HIV researchers have a more sophisticated understanding of their quarry than did previous generations of immunologists. "This is not very different from how vaccines generally are developed," she points out: "Everything is consistent with our enthusiasm."

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