AIDS Turnaround: Researchers Suddenly Upbeat over Vaccine

For the first time, many AIDS researchers appear confident that a vaccine is possible. The change in attitude is in large part due to recent success with monkeys. Thanks to an experimental new AIDS vaccine, monkeys at the Yerkes Regional Primate Research Center at Emory University infected with a lab-based amalgam of HIV and SIV (the monkey version of HIV) are living longer. Two other variations of the same approach are being tested at Harvard Medical School and Merck & Co laboratories -- with the same results.

Vaccine discovery has been notorious for its difficulty and clouded by doubts that such a thing is even scientifically possible. An AIDS vaccine is still no sure bet, scientists say, but many now believe that they are on a rational path toward finding one. "Suddenly there is a sense for the first time that perhaps we have the tools in hand today to make a substantial impact on the dynamic of the HIV epidemic," said Harvard's Dr. Norman Letvin. "Now there is an absolute stampede to get these technologies into humans and ask the question: Can we translate these monkey findings into the human situation?" How different humans are from monkeys is key and a matter of substantial debate among scientists.

Even with the new optimism, vaccine development is very slow. If the new research goes flawlessly, Dr. Harriet Robinson of the Yerkes Laboratory estimates that it will be 2005 before large-scale experiments begin with her vaccine. Learning whether it truly prevents AIDS will take another two years. "I ask myself whether it is justified based on the science," said Dr. Peggy Johnston, assistant director for AIDS vaccines at the National Institute of Allergy and Infectious Diseases. "And my conclusion is yes," she said.

One change in vaccine research is that scientists no longer seek to prevent infections. Yet, while the human immune system cannot turn back an HIV infection, new vaccines may be able to accomplish the next best thing -- train the immune defenses to hold the infection in check indefinitely.

HIV is a moving target. It mutates so fast that it constantly changes the proteins on its surface. Furthermore, the virus covers its surface with sugar, which hides its proteins from antibodies. As all of this became clear in the 1990s, scientists went back to basic questions. How is it, they asked, that people often live with HIV for eight to 10 years before falling sick with AIDS?

The answer turns out to be another line of defense against germs, the killer cells. Killer cells attack infected cells, antibodies attack only free-fleeting microbes. In the early days of infection, HIV burrows into its favorite target, the blood cell called the helper cell. The helper cell furnishes nutrients to the killer cells. As the helper cells multiply, HIV takes over their machinery forcing helper cells to produce HIV. Eventually, the killer cells awaken and destroy most of the infected cells before they can release the virus.

The battle is at first a stalemate. The virus is infecting helper cells and reproducing. Helper cells are nourishing killer cells, and killer cells are killing virus. Gradually, although the body produces new helper cells as fast as the virus ruins them, helper cells level off. Without a virus-killing drug to restore the balance, the result is AIDS and death.

"By doing relatively subtle things during the first hours to weeks of infection, we think we can have a dramatic payoff in allowing the body's own immune response over the long haul to contain this viral infection," said Letvin. Instead of dying from AIDS, vaccinated people who get infected may have a chance of living for decades or even a lifetime. Slowing the spread of the disease would also keep virus levels low, making people much less likely to pass on HIV.

Dr. Gary Nabel, director of the National Institutes of Health's Vaccine Research Center, said that even if the first versions are only modestly effective, tinkering will probably make them better. "We'll start with a Model T and hope to get to a Mercedes fast," he said.

Other vaccine development efforts include a more traditional vaccine already in final-stage testing. The AIDSVAX, by VAXGen has been given to 7,900 volunteers in the United States, Europe and Thailand.

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