San Francisco Chronicle - The Voice of the West, 901 Mission Street, San Francisco, CA 94119 - Wednesday November 21, 1990 Edition: FINAL Section: NEWS Page: A2 Word Count: 769
David Perlman, Chronicle Science Editor

Sixty men and women, all of them uninfected by the AIDS virus, will soon begin receiving shots at five university medical centers, according to officials at the National Institute for Allergy and Infectious Diseases, the leading federal AIDS research center.

If tiny doses of the experimental vaccine trigger no unwanted reactions, the doses will then be increased so that scientists can learn whether they can trigger the immune systems of the volunteers to mobilize antibodies against the injected substance.

Scientists have grown increasingly confident that developing a truly effective vaccine against HIV, the human immunodeficiency virus, is possible within the next few years, although none has yet reached an advanced stage of testing. Five other candidate vaccines based on various nongenetic manufacturing techniques previously were approved and are undergoing early trials in human volunteers in America.

The sixth and newest candidate vaccine is a genetically engineered combination of a protein and carbohydrate termed a glycoprotein. Its composition and structure precisely mimic the shape of one of the glycoproteins that is made naturally by the AIDS virus and that forms part of the outer viral coat. The protein is known as gp160.

EXACT MOLECULAR MATCHES

Earlier efforts at developing vaccines based on viral proteins to protect against other diseases have shown that matching the exact molecular shape of the proteins seems to be important, scientists say.

"In many cases, retaining the native shape of the viral molecule is crucial to a vaccine's ability to stimulate a strong immune response," said Dr. Anthony S. Fauci, director of the federal AIDS research agency. "We don't know if this is true for HIV molecules used in vaccines, but these new clinical trials will help answer this very important question."

CONFIDENCE BOLSTERED

And underscoring the confidence that vaccine researchers are now beginning to feel, Dr. James O. Mason, assistant secretary for health in the Department of Health Services said yesterday:

"This is an example of how recombinant DNA technology (genetic engineering) has revolutionized work in vaccine development, changing it from a relatively primitive science to an elegant art."

Research to develop the genetic engineering techniques for developing the new vaccine began several years ago in the laboratory of Dr. Bernard Moss, a leading virologist at Fauci's institute. Moss and his colleagues manipulated vaccinia virus -- the organism that is used in smallpox vaccines -- to carry the genes for various proteins into mammalian cells. The cells thus became miniature factories churning out large quantities of the proteins.

Scientists at the National Cancer Institute and an Austrian biotechnology firm called Immuno-AG then used the technique to make the AIDS vaccine material composed of the gp160 protein.

CHIMPS INJECTED

Two versions of the potential vaccine have been injected into four chimpanzees and "challenged" with doses of pure AIDS virus 100 times more than the amount needed to cause infection. The vaccine prompted an immune response in all the animals, and one of the chimpanzees has now been free of HIV infection for nearly three years, according to Dr. Martha Eibl, project director of the Immuno-AG firm.

NOT A VACCINE -- YET

Discussing the upcoming trials, Dr. Dani Bolognesi of Duke University, one of America's foremost AIDS vaccine researchers, cautioned that the new vaccine is still in its early stage of development.

"I don't consider it a vaccine as yet," he said, "because we need to know the human response." The enthusiasm of many vaccine researchers like Bolognesi is also tempered these days by concerns that a vaccine like this one, based on only a single protein of the AIDS virus, may never confer long-term protection against infection. The problem is more HIV, the virus that causes AIDS, comes in many different strains and is known to mutate frequently, thereby changing the nature of its proteins.

Ultimately, as Bolognesi pointed out, it is most likely that a successful AIDS vaccine will be a "cocktail" made up of many different viral proteins.

According to Dr. Robert Belshe of the St. Louis University Medical School, who will coordinate the human trials, all the volunteers for the first tests have already signed up and have been carefully screened to make sure that neither they nor their sex partners are at risk for AIDS. Later clinical trials, which may be several years away, will include people whose behavior defie trials will be conducted at Johns Hopkins, the University of Rochester and Vanderbilt University as well as at St. Louis, Belshe said.

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