Vaccine Protects Monkeys Infected With AIDS-Like Virus

      Harvard researchers reported today that a new vaccine combination, which suppresses an AIDS-like virus without wiping it out, has worked in rhesus monkeys.

      It is a small step with big implications in the campaign to curb the AIDS epidemic in poor and developing countries, where effective treatments are not available. Short of a cure, if a vaccine can reduce the infectiousness of the AIDS virus, the frightening spread of the disease in Africa and Asia might be slowed.

      The eight monkeys were immunized with a new vaccine followed by an injection of an immune system booster containing the genetically engineered protein interleukin-2. They stayed healthy despite infection with a laboratory variant of the AIDS virus that killed their cage-mates. Their immune systems remained intact, and the level of virus in their bloodstream was extremely low.

      This new approach might also afford patients already battling the disease with a means of keeping their immune systems functioning.

      "What we see is rather convincing evidence that, while we can''t prevent infection, we can change the course of clinical disease, at least in the short term," said Dr. Norman Letvin, a professor at Harvard Medical School and lead author of the paper published in today''s issue of the journal Science.

      Yet it would take a string of similar laboratory successes, and years and years of study, before today''s development could live up to its potential.

      The doctors tested a vaccine that is similar, but not identical, to one undergoing early safety trials in a small number of human subjects in the United States. Both the monkey and human vaccines were designed at the Pennsylvania-based Merck Research Laboratories, an arm of pharmaceutical giant Merck & Co. Inc., whose scientists collaborated with the Harvard doctors.

      "It is not what we hope to use in humans, but it is very, very close," said Merck spokesman Dr. Larry Hirsh.

      Most vaccines in use today -- preventing a range of scourges from smallpox to chicken pox -- stir up antibodies that can attack and neutralize invading viruses before they gain a foothold. The Merck experimental AIDS vaccine stimulates a different weapon, blood cells called CD8s, that seek out and destroy other cells already infected by the virus.

      The Harvard study shows that a strategy for stimulating this "cellular immunity" has worked in monkeys.

      But there are many caveats. It was a monkey experiment, with only a handful of laboratory animals involved. The vaccine tested is different from the one that would be used in humans, and the virus it tamed is a laboratory freak, closely related to HIV but not the same microbe that is causing AIDS.

      Nevertheless, the scientific rigor of the study has impressed AIDS researchers. "The results are really crisp, but what we don''t know is how long the protection will last," said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

      The study is an "important proof of concept," he said, but it remains to be seen if the idea will work in humans, or if the same beneficial effect would occur if the infection takes place long after the vaccine is given.

      Letvin said in an interview that the experiment was designed to speed-up in the laboratory the process in humans by which HIV infection progresses to AIDS. The rapid onset model gives researchers a tool to gauge early on whether a vaccine might work in the long run.

      The vaccine kept eight rhesus monkeys healthy for 20 weeks after they were infected with a version of the AIDS virus specially designed in the laboratory to infect and kill monkeys quickly. The laboratory strain, called SHIV, is made from the core of SIV, a virus that causes AIDS-symptoms in monkeys; and the outer shell of HIV, the virus that causes AIDS in humans.

      Five months into the study, seven of eight other rhesus monkeys that were not vaccinated had become ill with AIDS-like symptoms, and four of them died.

      The virus attacked and quickly destroyed the immune systems of the doomed monkeys. By contrast, the healthy monkeys showed a robust immune response.

      The key to survival of the vaccinated monkeys is that they also received booster shots of a stimulant called interleukin-2, that was designed to stir up a strong immune reaction to the vaccine. Four monkeys that were vaccinated but were not given the IL-2 did not fare as well -- their measure of infection-fighting white blood cells went down, and two became ill.

      Merck spokesman Hirsh cautioned that company researchers do not believe it is practical to use IL-2, an expensive and genetically engineered protein, in the field. But he said the company is working on other "adjuvants" that might produce the same beneficial effect.

      The most significant result in the Harvard monkey trials thus far is the data showing that the vaccine knocked down the level of virus floating in the bloodstream of the infected animals. Recent epidemiology studies have shown that the lower a person''s viral load, the less likely he or she will be to transmit the virus to someone else.

     

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