Immune Boost Found in AIDS Vaccine Trials
A French scientist who has repeatedly injected himself with a prototype AIDS vaccine has developed what appears to be the strongest human immunity yet achieved against the virus, it was reported today.
The development does not prove that the researcher, Dr. Daniel Zagury, a professor of immunology at the Pierre and Marie Curie University in Paris, is actually protected against the AIDS virus--because he has never been exposed to it.
Nevertheless, the researchers state, “Our results show for the first time that an immune state against the (human immunodeficiency virus) can be obtained in man.”
The report by Zagury and 16 co-authors is being published in Nature, a British scientific journal. Among the co-authors is Dr. Robert C. Gallo, the U.S. National Cancer Institute researcher who is a co-discoverer of the AIDS virus.
So far, the researchers said, Zagury has suffered no ill effects from the dramatic series of four self-injections that began in November, 1986, and continued through the fall of 1987. Laboratory tests on his blood also show that he developed a strong immune response against divergent strains of the AIDS virus. This has persisted for more than a year.
“We have overcome some pitfalls on the route toward a vaccine,” Zagury said in a telephone interview. “We by no means have yet a vaccine.”
The report cautions that the immunization procedures used on Zagury are too cumbersome to be tested on large numbers of people. “The protective effects of a candidate vaccine can only be tested in large-scale clinical trials (involving individuals at high risk of AIDS virus infection),” Zagury added. “What remains to be done is to find a preparation that mimics the same immune reaction as the prototype and that can be administered to thousands of people.” This would involve drastically simplifying the approach he has tested on himself.
In addition, crucial experiments to see if the test vaccine protects exposed chimpanzees against AIDS infection have yet to be completed. A vaccine suitable for widespread human use may not be produced for many years, if ever.
Zagury’s report appears to go far beyond the accomplishments to date of the two American groups also conducting preliminary AIDS vaccine trials in humans, at the National Institute of Allergy and Infectious Diseases in Bethesda, Md., and at the University of Washington School of Medicine in Seattle. And despite his image as a maverick figure, it places his laboratory at the forefront of mainstream AIDS research.
“He is the only researcher who has this kind of data in man at this point,” said Dani P. Bolognesi, a professor of surgery at Duke University who is collaborating with Gallo on AIDS vaccine research.
Dr. Bernard Moss of the National Institutes of Health said that Zagury has “shown that you get the expected types of immunity for a vaccine. The only thing that hasn’t been shown is that it protects (against the AIDS virus).” Moss provided the viral materials that Zagury has used in his research.
Vaccines, designed to protect healthy people from acquiring a disease, usually contain germs that are either live and non-toxic or dead. Once injected into the bloodstream, they work by inducing the body’s immune system to produce protective molecules called antibodies as well as special white blood cells that can eliminate foreign organisms. Thus, a successful AIDS vaccine would stimulate the body to protect itself against the AIDS virus.
Zagury’s approach uses a live-virus vaccine made with recombinant DNA technology, an approach also being taken by the Seattle researchers. A gene that produces a key AIDS virus envelope protein is inserted into the vaccinia, or cowpox, virus, which normally is used to immunize humans against smallpox.
This method has attracted widespread discussion among AIDS researchers. A live-virus vaccine is thought to stimulate a strong immune response and may be effective against multiple strains of the AIDS virus. But a serious drawback is the potential to trigger serious viral infections in recipients with weakened immune systems, unlike vaccines made from dead viruses.
Zagury’s latest paper expands on the initial report of his self-experimentation, published in Nature in March, 1987. It describes four different immunization techniques that were tested on a total of 14 volunteers in France and Zaire. Only one approach--that tested by Zagury on himself--elicited a strong immune response. None of the treatments generated toxic side-effects.
The laboratory evidence of immunity against the AIDS virus included the production of antibody molecules that blocked the ability of the virus to infect white blood cells and the activation of so-called “killer” white blood cells that destroyed cells that were already infected with the virus. It was present against very different viral strains. Such comprehensive evidence had not been reported previously.
One hundred days after Zagury first inoculated himself with the live-virus vaccine, he received an intravenous infusion of his own white blood cells. Those cells previously had been removed from his body, infected with the live-virus vaccine in the laboratory and then chemically inactivated. This unwieldy procedure was apparently the key step in triggering the strong immunity.
More than six months later, when AIDS virus antibodies could no longer be detected in Zagury’s blood stream, he received a small dose of the AIDS virus envelope protein underneath the skin. (The procedure is similar to a widely used test for exposure to the bacteria that causes tuberculosis.)
Within an hour, a 1 1/2-inch area of redness and swelling developed and after two days a smaller pimple. This indicated that Zagury had developed “immune memory cells” that could trigger a protective response when exposed to a portion of the AIDS virus. Other volunteers who served as controls had no reaction to the small dose of the envelope protein.
After this experiment, Zagury received two large booster injections of the purified AIDS virus envelope protein, which further enhanced his persistent immunity.
As of the end of March, more than 85,000 AIDS cases had been reported to the World Health Organization, which is about half the cases estimated to have occurred since AIDS was first recognized as a fatal disease in the early 1980s.
