PUTTING HIS TRUST IN SALK\Testing to begin on AIDS drug.

Byline: Keith Stone Daily News Staff Writer

He isn't sure why, but he is among a rare, mysteriously fortunate number of people infected with the human immunodeficiency virus for more than a decade who show no overt symptoms of AIDS.

Jay Rosenthal also is among a rare number who refuse to take AZT, ddI or any other government-approved anti-AIDS drugs.

Rosenthal just doesn't trust them.

Now Rosenthal wants to roll up his sleeve this week at a Los Angeles clinic for a shot of a vaccine pioneered by Dr. Jonas Salk - the same man who survived his critics to end polio's paralyzing scourge in 1955.

Salk's therapeutic vaccine won't cure AIDS or ward off infections. The study that begins today - the first of its kind in the United States - will determine whether the drug can prolong life and slow the virus's attack.

Rosenthal says he is entrusting his life to the Salk legacy.

"He's had a pretty good track record," the 43-year-old Beverly Hills man said last week. "You are going to believe somebody who has done as well as he's already done."

Whether the Salk vaccine proves its worth won't be known for three years, the time it will take to test 3,000 people, half of them with a placebo.

And already, leading AIDS researchers and activists question whether the manufacturer is wasting its money - more than $50 million - to test a drug that has shown only subtle promise.

"If we were paying for it," said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, "I can tell you it wouldn't have gotten this far."

Such criticism is not new for The Immune Response Corp. and its Remune vaccine; company officials assert that their drug is freighted unfairly by both Salk's radical approach and his reputation as an iconoclast.

"We haven't been a favorite of our government. Maybe it goes back to Jonas," said Richard Trauger, chief scientific officer for Immune Response, based in Carlsbad.

Salk will never know whether his brainchild will succeed: He died in June at 80, nearly nine years after proposing that the lessons he learned in the fight against polio could be employed against AIDS.

Salk believed he could jump-start the immune system by coupling an altered, killed, HIV with a chemical the body would recognize as a foe.

Used to treat an HIV infection - not to prevent and eliminate it - the Salk vaccine is the first such vaccine to reach what the Food and Drug Administration calls Phase III trials, the final test to see whether a drug should be sold.

The FDA approved the nationwide study largely based on findings from an earlier experiment and an advisory panel's reluctant endorsement.

The results in the earlier test, published in the Journal of Infectious Diseases, showed that Salk's vaccine slowed the rise of HIV in the body, delayed the destruction of immune system cells and boosted other immune reactions.

These are subtle improvements, researchers say. By contrast, more dramatic effects are found in people treated with anti-AIDS drugs that attack the virus directly. Indinavir, approved just last week amid much anticipation, has been shown to cut the amount of detectable HIV by 80 percent to 90 percent when used alone.

However, Trauger says he believes the Salk vaccine will remain useful long after the AIDS virus develops resistance to Indinavir and other more conventional anti-AIDS drugs already on the market.

"Everybody said it won't work, it won't work. But he did it anyway - and it worked," Trauger said. "He would not give up. It is really going to be a great thing to get this off the ground, to fulfill his dream to get this tested."

"This therapy is very safe. It is very easily tolerated. It has clearly shown impacts," Trauger said.

The chairman of the FDA advisory committee, Dr. Stanley Lemon, is not optimistic about the vaccine but said he found no reason to forbid human trials.

"My guess is that this vaccine will be tested and will be shown to have no objective therapeutic benefit," said Lemon, a University of North Carolina immunologist.

Project Inform founder Martin Delaney, whose activism has helped influence the government's and the drug industry's response to AIDS, also said he has little hope for the Salk vaccine.

"The only reason this was going forward is because this was a company with a name on it, with the money to make it go forward," he said. "You should be pouring more of that money into better vaccines."

According to Lemon, Salk's reputation played a minor role, if any, in the decision to approve wider testing.

"Dr. Salk commanded a lot of respect for his achievements with polio," Lemon said, "but I don't think that contributed substantially to what the committee decided."

Immune Response also suspects that the vaccine is a victim of lingering bias against Salk's killed-virus approach - a prejudice that dates back to the advent of Salk's polio vaccine.

Shortly after people began using the polio vaccine, a drug manufacturer mistakenly left live virus in a batch, causing several cases of polio. Use of the vaccine was stopped until the problem could be found.

And then, in 1969, Salk's vaccine was replaced almost universally by one developed by Dr. Albert Sabin.

"Controversy is part of this product," said Steven Richieri, senior vice president of operations for Immune Response.

In the end, even Salk's doubters concede that they don't know exactly how the Salk vaccine will function in long-term testing.

"There are many examples of people who have cut across the grain and done things that didn't see appropriate at the time," said University of Michigan researcher Dr. Gary Nabel. "I wouldn't be too critical of them going forward."

Added Nabel: "It is important to recognize in any of these trials, we are up against a sizable foe."

And HIV is not the only enemy.

Last week, a blue-ribbon panel of scientists and community activists concluded that the push for an AIDS vaccine in the United States is failing and in dire need of an overhaul.

The 114-member panel, including Nobel laureates, called for the National Institutes of Health to cede authority to non-government scientists in the hunt for a vaccine.

"The development of a safe and efficient vaccine to prevent HIV infection is among the highest priorities for the AIDS research effort," according to the NIH-sponsored report.

"Yet, vaccine research historically has received less funding and attention than other areas of AIDS research," the report says.

This year alone, the National Institute of Allergy and Infectious Diseases plans to spend $557.7 million on research, including $36.7 million - or 6.4 percent of its budget - on vaccine clinical trials.

In the 13 years since Los Angeles doctors identified the world's first cases of AIDS, only about 20 vaccines have been tested on uninfected humans. None of them have caused infection, but none have been shown to prevent it, either.

NIAID director Fauci says the lack of vaccines is due simply to a lack of good ideas, not bureaucratic or financial obstacles.

"The science has not been there," he said.

Clearly frustrated, Fauci issued a report in November, outlining his strategy for vaccine development. In it, he concedes, "Market forces do not foster a desirable level of private sector activity in vaccine research and development."

And the government does not, either, according to some company researchers.

NIAID's decision not to finance a widespread study of Genentech's gp120 vaccine has left Fauci and company researcher Don Francis trading accusations of scientific bigotry and profit-driven bias.

"I don't think we give a damn about prevention," said Francis, who came to Genentech after helping steer the federal Centers for Disease Control and Prevention through the early years of the epidemic. "We'd rather get magic bullets. We are centered around therapy."

Overshadowing the vaccine debate is the cost of developing a drug and the risk of liability presented by vaccines.

It can take from 12 to 15 years to bring a drug to market, at a cost of $359 million, according to the Pharmaceutical Manufacturers Association.

"If I were a chief executive officer of a company, I'd have to be sent off to a funny farm to get my company involved in AIDS vaccines," said Dr. John Siegfried, the group's associate vice president for medical and regulatory affairs.

At pharmaceutical giant Merck & Co. Inc., Dr. Gordon Douglas, president of the vaccine division, said he sees the day when people will be immunized against AIDS.

"It is a tough business," he said, "and it isn't big enough for hundreds of companies."

Jay Rosenthal is betting on Salk.

"Obviously you remember the inventor of this vaccine that saved all of these people," he said.

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PHOTO

(1 -- color) Jay Rosenthal will be taking part in trials of a therapeutic AIDS vaccine developed by the late Dr. Jonas Salk. Terri Thuente/Daily News (2 -- color) Immune Response employees Chris Migliaccio, left, and Cliff Severn suit up for work. Hans Gutknecht/Daily News