San Francisco Chronicle - FRIDAY, December 18, 1992
Charles Petit, Chronicle Science Writer

The monkeys became resistant to an AIDS-like disease after researchers injected them with genetically hobbled, but living, versions of a virus that usually gives the animals a fatal AIDS-like disease.

Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, which oversees basic federal research on AIDS, called the results with monkeys a "significant advance" toward an AIDS vaccine. In three years of research at the Harvard Medical Center's New England Regional Primate Center in Southborough, Mass., four rhesus monkeys were first inoculated with a living but genetically altered version of the simian immunodeficiency virus or SIV. It closely resembles the human immunodeficiency virus, which causes AIDS in people, and it similarly wrecks the monkeys' ability to fight disease.

During the next two years, the animals came out unscathed after 10 exposures to large doses of normally virulent SIV. A few weeks ago, three years after vaccination, two of the monkeys got the equivalent of 1,000 doses of the simian virus, again without ill effect.

The animals developed a very low level of infection but no sign of disease or reduction in immune function. Their T-cells, the immune components hardest hit in both human and monkey AIDS, remained at normal levels.

Of 12 "control monkeys" given similar doses of SIV since the tests started, but not vaccinated with the "attenuated" or weakened version first, 11 have died.

The report, by a group led by Ronald C. Desrosiers, is published in today's issue of the journal Science.

The live virus vaccine is different from other AIDS vaccines in more advanced stages of development. The usual practice is to inject small fragments of the virus, usually isolated proteins commonly found on its outer coat. The hope is to train the immune system to attack strongly any whole, living viruses that it encounters.

NO HUMAN TESTS

The new method is not ready for human tests and could cause difficulties for blood screening and for making sure that the vaccine itself poses no danger. Vaccines with modified AIDS viruses might leave the vaccinated person with antibodies in their bloodstreams that would appear in blood screening tests exactly like signs of AIDS infection.

More important, vaccines from live viruses, even with some of their genes removed, could pose immense quality control problems to be sure that the vaccine is harmless. Furthermore, the weakened virus might mutate or revert to a dangerous form.

An analysis accompanying the report quotes Desrosier as saying that "it will take 10 or 15 years of safety testing before we can be comfortable putting this into thousands of people."

Even if a live virus vaccine for AIDS is slow in development -- or never emerges at all -- the new results boost faith that the body does have the latent power, if properly harnessed, to resist AIDS infection. It also may provide clues to how to engineer other forms of vaccine that are more effective than those nearing human trials now.

Despite potential drawbacks, "This SIV vaccine has given the first indication of truly strong protection" against diseases caused by so-called retroviruses, said Margaret Johnson, associate director for AIDS research at the National Institute of Allergy and Infectious Diseases.

UC DAVIS RESEARCHER

Dr. Murray Gardner, professor of pathology at the University of California at Davis, said researchers there expect to begin testing the same vaccine on monkeys.

In addition, Gardner said, some of the monkeys from the New England study will be brought to Davis to be put among other SIV-infected monkeys to determine whether they continue to resist the disease.

The Harvard team discovered the powerful monkey AIDS vaccine almost by accident. To study how the simian virus works, they genetically altered some of the viruses to watch the effect. In one version, they removed a gene called "nef," whose function is unclear. The modified virus did infect monkeys, but only at a very low level, and it seemed to cause no illness. Only then did the researchers start to wonder whether they had stumbled onto a safe vaccine.

There is no full proof, but many AIDS researchers have said that although people with HIV infections seem to be unable to stamp out the original virus that infected them, they seem to resist infection from subsequent exposures to the many strains of HIV. Hence, a low-grade infection of harmless HIV might arm the body against more dangerous forms.

The live-virus technique is an old one in medicine. Early vaccines against smallpox, as well as polio, relied on inoculation with live but weakened strains of usually virulent viruses.

The new report "is not all that surprising, really, because in the history of vaccination, attenuated viruses always work best," said Gardner at Davis. The new results, he said, "are far and away the best we've seen" in the five years that people have been testing possible AIDS vaccines.

Always watch for outdated information. This article first appeared in 1992. This material is designed to support, not replace, the relationship that exists between you and your doctor.

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