AIDS Wins This Round.

For more than a quarter-century, the medical community has been trying to develop a vaccine against AIDS--and for more than a quarter-century, it has been disappointed. Earlier this year, it seemed that science had its best shot yet, with a large trial of a new vaccine that would use a novel strategy to protect the body against HIV. In September, however, the results were announced, and this vaccine too had failed. Its developer, Merck, has now released an analysis of the trial, and while the vaccine performed as poorly as reported, the reasons it failed provide insight into what might make it succeed next time.

Most vaccines work by exposing the immune system to a weakened or killed virus, which sensitizes the body to the bug and causes it to produce a standing army of antibodies. If a viable virus presents itself later, the antibodies signal immune-system cells, which engulf the invader. AIDS vaccines have never produced a crop of antibodies robust enough to get this defense going.

The Merck vaccine used a different approach, called cell-mediated immunity. Scientists inserted three HIV genes into an ordinary cold virus and injected it into the body. Immune-system dendritic cells would, it was hoped, gobble up the virus and then display its gene markers--along with those of the HIV. This would teach the immune system's T cells to recognize and kill AIDS-infected cells.

What should have happened, however, didn't, and the vaccine provided no real protection. "I don't think anyone imagined the results would be so definitively negative," says Dr. Gary Nabel, director of the Vaccine Research Center at the National Institutes of Health.

One explanation might be that the scientists chose a cold virus as the delivery vehicle. Cold viruses do a good job of ferrying HIV genes for the same reason they do a good job of making us feel lousy: once inside the body, they infect cells very efficiently. But they are so common most people have some tolerance to them, and so the immune system waves them past without getting too excited by them--or by any HIV genes that might be riding piggyback.

A possible solution would be to stick with the cold virus but use different HIV genes and two injections spaced a few months apart. Dr. David Ho, director of the Aaron Diamond AIDS Research Center in New York City, thinks the answer might be to abandon the cold virus and switch to another one, perhaps chicken pox. HIV won yet another round, but the game is long--and science is patient. How an aids vaccine could work [This article contains a complex diagram. Please see hardcopy of magazine.] 1 A cold virus has been engineered to carry three synthetically produced HIV genes 2 Dendritic cells in the immune system absorb the virus and display the HIV gene product on their surface 3 T cells then learn to recognize those HIV markers on dendritic cells and become sensitized to them 4 Should a cell infected with the real AIDS virus present itself later, the cells are primed to attack it directly