SAN FRANCISCO CHRONICLE (SF) - MONDAY August 15, 1988 Edition: FINAL Section: NEWS Page: A2 Word Count: 1,342
David Perlman, Chronicle Science Editor

Now, more than four years later, no scientist will predict any date for achieving a vaccine, and a safe, effective vaccine is believed to be more than a decade away.

Although progress is reported almost weekly, daunting questions still overwhelm the search for a vaccine, and only a few tentative answers have emerged so far.

Whether the scientists ever succeed in producing immunity against infection by the virus, or in weakening the organism when it attacks, the quest is proving to be the most difficult challenge in the history of immunization.

"The scientific and public policy challenges are formidable," say Wayne Koff and Daniel Hoth, two leaders of the vaccine search at the National Institutes of Health. They note that major unknowns about the basic mechanisms of immunity remain to be solved, and questions of ethics, risk and cost must ultimately be resolved.

"I'm an optimist," says Dr. Jay A. Levy, a physician and AIDS virus researcher at the University of California at San Francisco. "But we've got a long time to wait. I don't make predictions, but I'm saying we won't have a vaccine until well past the year 2000."

The painful search for an AIDS vaccine stands in marked contrast to the success that has been achieved in producing immunity from such other scourges as polio, smallpox and hepatitis.

Smallpox has now disappeared from the world, thanks to a vaccine discovered nearly 200 years ago. Polio has been conquered wherever the names of Salk and Sabin are known. Hepatitis-B is succumbing to a new vaccine developed through the high-tech methods of genetic engineering.

SCIENTIFIC OBSTACLES

But the road to an AIDS vaccine is barred by a number of unique and painfully frustrating obstacles:

-- The virus is an unpredictable chameleon. At least two distinct varieties, HIV-1 and HIV-2, have been identified, and evidence from infected individuals shows thousands of variations in the genetic code of the virus. Mutations constantly change the protein molecules on the outer coat of the virus, and vaccine-hunters know of only a few that might prove stable enough to exploit in an effort to mobilize immunity.

-- No single animal has been found that can serve as a model system to test the possible approaches that might yield a vaccine. Chimpanzees can be infected by HIV, but they do not get the disease. Rhesus monkeys get an AIDS-like disease, but it's not the same as human AIDS. Sheep, goats, horses, cows and cats can all get diseases caused by retroviruses - the broad class of organisms that includes HIV - but the diseases are vastly different from AIDS.

-- Recent findings suggest that some antibodies to the AIDS virus, which would be mobilized by a vaccine in order to neutralize the virus, may actually turn out to enhance infection rather than battle it.

-- The AIDS virus can remain latent and inactive in the human body for months or years after infection, so no one can predict how long it might take to determine whether or not a potential vaccine is truly effective.

PRACTICAL ISSUES

Even more disturbing are the practical questions that will arise if and when the scientific puzzles seem to have been solved.

Specialists in medical ethics, insurance experts for pharmaceutical companies, government cost-accountants in the health services, and laboratory chiefs who design the protocols for vaccine tests face problems of unprecedented magnitude. Their discussions fill the agenda of conferences and the pages of technical journals as they pose their questions:

-- Would uninfected people who are not at risk for the disease volunteer to be vaccinated in a large trial? If they were vaccinated would it be ethical for doctors to infect them with the deadly AIDS organism, knowing the vaccine's safety was still unproven?

-- If high-risk people volunteer - homosexuals who do not practice safe sex, for example, or prostitutes, or intravenous drug users - wouldn't doctors be morally bound to counsel them on how to avoid exposure, and thereby muddy any data on a vaccine's presumed effectiveness?

-- Because all vaccine trials require detailed record-keeping, how would the confidentiality of volunteers be assured? Anyone vaccinated would develop antibodies to the AIDS virus and would then test positive for infection even though the person might actually be protected against infection. What would be their status in society if their anonymity were breached and how would their subsequent ability to obtain health insurance be affected?

In the history of immunization, most vaccines have been discovered only after detailed study of people who recovered from infection and disease without any treatment at all. In such cases, their natural immune responses served as models that led scientists to the vaccine. And there lies yet another major difficulty in AIDS:

"No such model exists for HIV, because no one has yet recovered from the disease," says Dr. Anthony Fauci, coordinator of AIDS research for the National Institutes of Health. Besides, Fauci points out, "scientists still do not fully understand the nature of an effective immune response" when the AIDS virus attacks.

As the vaccine hunt is pressed, urgent logistical questions are also arising.

MANUFACTURING PROBLEMS

Eventually, drug companies will have to make the vaccine, and already fewer and fewer pharmaceutical firms are manufacturing vaccines of any sort because they fear multimillion-dollar liability lawsuits.

A new California law protects manufacturers of AIDS vaccines approved by the Food and Drug Administration from strict liability for unavoidable risks within this state.

But the California law does not protect firms against liability during approved clinical trials, and there is no federal legislation at all. Many drug company executives say they would not seek to test or market a vaccine even if one were developed unless Congress passed special legislation making the government liable for damages.

SIGNS OF PROGRESS

There have, to be sure, been some signs of progress, and different approaches to vaccine development are being actively researched by commercial biotechnology companies. Three are being tested in humans and another - which is not actually a vaccine but is designed to boost the immune response in people already infected by the AIDS virus - is also undergoing human trials.

The federal AIDS program at the National Institutes of Health recently committed nearly $6 million for grants to a half dozen vaccine developers this year, and that sum is expected to multiply annually from now on. "The benefits to society of a safe and effective AIDS vaccine outweigh all of the scientific, economic, social and political risks associated with vaccine development," say NIH researchers Koff and Hoth.

For Jay Levy at UCSF, none of the varied efforts now under way are likely to succeed.

"We'll solve the problem only after we've gotten rid of every obvious approach because we will have to look for new and novel ways of creating a vaccine," he said recently. "But somehow, I'm sure, we'll find the right approach, even though we don't yet know what it will be."

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CHART: AIDS VACCINE PROJECTS

Developers Status

Biotech Research Labs, Early research Rockville, Md.

Chiron Corp., Emeryville First human trials & Ciba-Geigy, Summit, N.J.

University of Southern Continuing human trials

California & Salk Institute, La Jolla Genentech, South San Francisco Early research

Cambridge Bioscience, Worcester, Mass. Early research & Institut Merieux, Lyons, France

MicroGeneSys, West Haven, Conn.& National Institutes of Health Continuing human trials

University of Washington & Oncogen Co., Seattle First human trials

Otisville BioPharm, Otisville, N.Y. Early research

Repligen, Cambridge, Mass. & Merck & Co., Rahway, N.J. Animal studies

Viral Technologies, Washington Applied for human trials

Wistar Institute, Philadelphia Applied for human trials

Source: Pharmaceutical Manufacturers Association

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PHOTO CUTLINE: (1) 'I'm saying we won't have a vaccine until well past the year 2000,' said Dr. Jay Levy of UCSF / PHOTOS BY ERIC LUSE/THE CHRONICLE, (2) DR. ANTHONY FAUCI / Coordinator of AIDS research

CAPTION: PHOTO (2), CHART: SEE END OF TEXT

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