Newsday - June 20, 1989
Laurie Garrett

"It's very difficult to get a vaccine," HIV co-discoverer Luc Montagnier of France's Pasteur Institute said at a news conference at the recent Fifth International Conference on AIDS in Montreal. "My guess is maybe in five to ten years we can get something that looks promising, that would give short-term protection. But all efforts to date are very disappointing," he concluded.

Dr. Jonas Salk, inventor of the original polio vaccine, drew a lot of attention at the conference when he announced the latest details on his entry to the AIDS vaccine competition, but neither he, nor the dozens of other researchers in the field, was able to raise a significant immune response in patients given the potential vaccine.

Nine years after the epidemic began, researchers are now recognizing that the key to both understanding and defeating AIDS may rest with the body's disease-fighting immune system.

For a vaccine to succeed it must be able to imprint upon the body's immune system the "memory" of the virus. If the cells of the immune system have "seen" the virus in some form before and "remember" it, the system will mount a strong response when natural infection occurs. Antibodies, specifically targeted to human immunodeficiency virus, which causes AIDS, will surround the AIDS virus, both incapacitating the invader and alerting other forces in the system to mount an attack.

So far, no research team has found a vaccine that can trigger the cascade of responses necessary to fend off HIV infection, and scientists are becoming increasingly concerned that HIV may prove impossible to tackle by traditional vaccination approaches.

Jacques Homsy and Jay Levy of the University of California in San Francisco announced in Montreal the discovery of antibodies, produced by HIV-infected individuals, that actually help the virus. Rather than fighting off HIV, these antibodies form bridges that allow the virus to enter cells, including those that lack the CD4 markers previously believed to be necessary for HIV infection.

Robert Gallo of the National Cancer Institute, co-discoverer of HIV, denounced claims that the virus can infect cells of the brain, immune system, gut and skin that do not bear CD4 markers, calling the research "test-tube aberrations." But if, indeed, these are aberrations, they are widely seen in dozens of laboratories throughout the world, according to 15 presentations at the international conference.

Levy issued what he termed "a strong warning for potential vaccine programs," noting that he can remove virus from an infected, asymptomatic patient, mix it in a test tube with a patient's blood and observe a strong immune response that kills the virus. But, he warned, if that same viral strain infects another person, is withdrawn and mixed in a test tube with the original patient's blood, the immune system does not respond.

Jean-Claude Gluckman of the Pasteur Institute in Paris reported similar findings. Levy and Gluckman said the virus is picking up sugar molecules from the human cells it infects, sugar-coating itself in a disguise that eludes the immune system. This process, they said, can be repeated indefinitely by the virus.

Based on this and other discouraging news, Montagnier said, "it is useless to think of vaccines against the HIV virus which are made by using virus products." All vaccines now under development are made from portions of the HIV virus.

Due to frustration over attempts to find a vaccine against HIV, researchers are increasingly shifting their focus to developing a better understanding of how the body reacts to infection with HIV. Even virologists now say the majority of the damage seen after HIV infection is actually the result of the immune system wreaking havoc upon itself. "I think we must admit," said Montagnier, "that perhaps the host [human] factors are more important than the viral factors."

For example, several research teams presented evidence that immune cells known as macrophages, when infected by HIV, secrete a plethora of special chemicals. These chemicals, which normally regulate the body's disease-fighting system, flood the blood system in inappropriate levels, sending a variety of incorrect signals. One such chemical, according to scientists from the Pasteur Institute, directly blocks the production of antibodies against the virus. Another, according to a report from the University of California in Los Angeles, promotes the growth of Kaposi's sarcoma tumors, which are commonly seen in AIDS patients.

Levy said that the most crucial problem in the immune system following HIV infection is the loss of a special type of cell called CD8. Numerous laboratories reported at the conference that decreased CD8 levels directly correlate with the progression of the disease.

Indeed, Levy and colleague Chris Walker said they have discovered that some HIV-infected individuals, yet to develop symptoms, make CD8 cells that directly kill HIV. "If we could get CD8 responses back to an appropriate level," said Levy in an interview, "we could keep the asymptomatic individual free from progression to clinical symptoms."

And it may be possible. Just last week the U.S. Food and Drug Administration gave Levy's colleague, Dewey Moody, permission to remove CD8 cells from AIDS patients, grow the ones that kill the virus, and then inject the killer cells back into the patients. And Jan Brinchmann of the National Hospital in Oslo, Norway, has verified the Levy findings and demonstrated these CD8 cells secrete a chemical that kills HIV. Work is now under way on isolation of that chemical.

"Let's find something that will enhance CD8 cells," said Levy, "or mimic the factor released by these cells, and you'll have a nice drug [for AIDS]." Levy hopes he will find the HIV-killing factor in the blood of several San Francisco men who have been infected, but asymptomatic, for several years. One has carried the virus and been disease-free for six years. "These people," said Levy, "are the hope for the future."

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Developing a Vaccine

Experts say it would probably take as long to develop an AIDS vaccine as the 18 years it took to create a gentically engineered vaccine against hepatitis-B. Below are the steps - and time - involved in the case of hepatitis vaccine. The search for an AIDS vaccine is in Stage I.

Stage I: Selection of the proper material for a vaccine

1968-1978

Time: 10 years

Stage II: Development of the proper solution used to carry the vaccine, which is injected

1978

Time: 1 year

Stage III: Developing the ability to mass-produce the vaccine

1979-1980

Time: 2 years

Stage IV: Purification of the vaccine to guarantee safety

1980-1984

Time: 4 years

Stage V: Preclinical tests in animals and small groups of humans.

1984-1985

Time: 2 years

Stage VI: Clinical trials on large groups of humans

1985-1986

Time: 2 years

Stage VII: FDA approval and licensing for general use

1986

Time: 1 year.

SOURCE: Dr. Dani Bolognesi, Duke University

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