Closer to an Aids Vaccine?

By Claudia Wallis.

It is the quick-change artist of the microbe world, a virus that minutely alters its external make-up, dozens of times as fast as the influenza bug. The rapid evolution of the deadly AIDS virus is a source of wonder to scientists. "We have not yet seen two viruses that are identical from two patients," says Dr. William Haseltine, a leading AIDS researcher at Harvard. Where did the deadly germ come from? Did it evolve from a less harmful variety? Last week reports from both sides of the Atlantic offered clues to the origins of the virus that causes acquired immunodeficiency syndrome. More important, they suggested new approaches to stopping and preventing the disease, which has struck more than 18,500 Americans and killed nearly 10,000.

Especially hopeful news came from the laboratory of Dr. Myron ("Max") Essex at the Harvard School of Public Health. Addressing a meeting of the American Society for Microbiology in Washington, Essex announced that he, together with colleagues in Senegal and Tours, France, had isolated a new virus that is "closely related" to the AIDS virus but has several significant distinguishing traits. The virus, which was isolated from blood samples taken from Senegalese prostitutes, is structurally similar to the AIDS virus but even more closely connected to a virus that infects certain African monkeys. Says Essex: "We believe it is a missing link" between the two.

The most exciting feature of the new virus is that it appears to be harmless. In the lab, says Essex, it behaves much like the AIDS virus, infecting the same immunological cells (helper T cells) but without the "dramatic killing action" of its lethal cousin. None of more than 50 people infected with the virus have developed any symptoms of AIDS. Thirty have been followed for more than a year and have remained healthy, but, says one of Essex's collaborators, Francis Barin of the virology laboratory of Bretonneau Hospital in Tours, "we must wait for more time to pass to be certain." Barin and Essex are hopeful that the new virus could serve as a natural vaccine, protecting those it infects against the more harmful AIDS virus, much as people infected with cowpox virus are protected against smallpox. Studies of old blood samples indicate that the virus has been present in Senegal for at least ten years. Significantly, no cases of AIDS have been reported in the country, though the disease is rampant in central Africa.

Shortly before Essex revealed his discovery, a group of French and Portuguese researchers announced a related finding. At a conference in Lisbon, Dr. Luc Montagnier of Paris' Pasteur Institute disclosed that his team too had found a missing-link virus, apparently closer to the simian virus than it is to the human AIDS strain. As in Essex's study, the new virus was found in the blood of West Africans -- in this case, two men from Guinea-Bissau, which borders Senegal. Both men, however, were suffering from the symptoms of AIDS. "It seems to be the same disease; there was nothing peculiar about their illness," says Dr. Francois Clavel of the Pasteur team. The new virus, however, is sufficiently different from the AIDS virus that it is not always detected by current blood-screening tests for AIDS, says Clavel. But he believes that the risk of contaminating banked blood is small, since the virus appears to be rare.

The close timing of the two announcements was no accident. A heated rivalry has raged between French and American researchers for two years; Montagnier and Dr. Robert Gallo of the National Cancer Institute each claims to have been the first to discover the AIDS virus. Bickering aside, both new findings help confirm the theory that the AIDS virus evolved from a microbe that commonly infects African green monkeys, apparently causing them no harm. Essex's team identified the monkey virus last year and speculated that it had first spread to humans who ate monkey meat or were bitten by the animals. Somewhere along the line, Essex hypothesizes, the virus mutated into the lethal AIDS-causing form. His newly discovered strain might be one of several intermediate forms that arose as the virus mutated. Says Essex: "I predict there will be other viruses in the spectrum."

The news of an apparently harmless relative of the AIDS virus was greeted with enthusiasm by other scientists. "The best thing about Max's virus," says Gallo, "is that we can learn why one is pathogenic and the other isn't." By identifying which component of the AIDS virus is responsible for its deadly effects, researchers may be able to develop new drugs that specifically inhibit it. They may also be able to alter the virus genetically to remove its harmful traits, leaving a benign version that could serve as a vaccine.

Late last week research teams in both Gallo's and Haseltine's laboratories revealed that they had already succeeded in tinkering with the AIDS virus and rendering it inactive. They did so by snipping out a gene that enables the virus to replicate with remarkable speed. Without the gene, the viruses "don't kill T cells and don't reproduce anymore," says Haseltine. The "dead-ended" virus, he notes, could serve as a prototype for a vaccine.

Unfortunately, there are many obstacles to a truly workable vaccine. Safety is one: even a genetically altered virus could conceivably cause disease. A successful vaccine would have to trigger the production of antibodies that protect the individual against AIDS; most AIDS patients have antibodies that, for some unknown reason, fail to protect them. And in light of the changeability of the AIDS virus, the vaccine would have to offer immunity against an almost infinite array of variant strains. No virus has presented vaccine makers with more formidable challenges. But given the lightning pace of discovery, says Essex, "we will likely know within a year or two whether or not a vaccine will be feasible."

With reporting by Andrea Dorfman/Washington and