Los Angeles Times (LT) - FRIDAY June 11, 1993 Edition: Home Edition Page: 6 Pt. A Col. 1 Word Count: 801
Sheryl Stolberg; Times Medical Writer

Until now, most researchers have shied away from so-called "live attenuated vaccines," believing it would be far too risky to inject humans with even a crippled form of the deadly human immunodeficiency virus. The World Health Organization decision, disclosed this week at the Ninth International Conference on AIDS here, is intended to prod researchers to aggressively pursue such preventive vaccines--and governments to fund the work.

"It was a big decision," Dr. Jose Esparza, chief of vaccine development for WHO's Global Programme on AIDS, said in an interview Thursday. "There is an instinctive reaction of people to say no to vaccination with (the live AIDS virus). . . . There are concerns, and they should be addressed. But the reaction to that concern should not be to say no."

But several prominent AIDS experts expressed skepticism, and at least one is vehemently opposed to the idea.

"This is an extremely hazardous proposition, in my mind," said Dr. Robert C. Gallo, an expert on retroviruses who is the co-discoverer of HIV. "I feel I have to speak out against it. . . . The risk is astronomical."

Anthony Fauci, a respected scientist who is also the top AIDS official at the U.S. National Institutes of Health, said the U.S. government is not opposed to financing research on live-virus vaccines. But, he said, top priority will continue to go to safer genetically engineered vaccines, which are formulated using only a protein from the virus's outer membrane, or "envelope," and thus carry no risk of infection.

But the World Health Organization, which based its decision on the recommendation of a panel of scientists who convened last week at the headquarters of the U.N. agency in Geneva, has a different mission from that of the U.S. health organization. The global agency must concern itself with the rapid spread of AIDS in the developing world, which accounts for more than 80% of HIV-infected people.

Esparza said live-virus vaccines would probably be cheaper to manufacture than those that rely on sophisticated genetic engineering techniques, making them more suitable for distribution in nations such as Thailand, Uganda, Rwanda and Brazil--the four countries targeted by the U.N. agency for clinical trials when a vaccine is eventually developed.

However, this raises concerns that Third World people could be used as guinea pigs to test the potentially dangerous live-virus vaccines, while the safer and more expensive products would be tested in the United States.

"I think ethically speaking, if (a live-virus vaccine) is developed in the U.S., it perhaps should be tested in the U.S.," said David Ho, director of the Aaron Diamond AIDS Research Institute in New York. "Otherwise everyone involved is going to be accused of taking advantage of a developing country."

The notion that a live-virus vaccine could work for AIDS captured the attention of the scientific community in December, when Harvard University researcher Ronald Desrosiers reported that he had inoculated four rhesus monkeys with a weakened form of the live simian immunodeficiency virus--SIV, the monkey version of HIV--and that they had remained immune for more than three years.

The monkeys are still immune; this is the longest-lasting, strongest protection ever achieved in any such AIDS experiment. Meanwhile, researchers in London and France have duplicated Desrosiers' work and have reported their results this week in Berlin.

The live-attenuated method is a classic technique for developing vaccines. The polio vaccine developed by Dr. Albert Sabin, widely used in North America, employs this method. So do vaccines for smallpox, measles and flu.

These vaccines are preferred because they generally provide very strong immunity. Without causing disease, they create an infection inside the body that prompts the immune system to fight back.

But at the same time, they carry a tiny risk, the possibility that the weakened virus could revert to a form that would cause disease. The Sabin vaccine causes polio in an estimated two out of every 1 million people vaccinated.

With HIV, Gallo and other experts say, that risk increases dramatically. AIDS is a retrovirus, meaning it inserts its genetic blueprint into the cells of the person infected. Unlike polio or measles or smallpox, the virus will never fade away after a person is vaccinated.

Rather, the genetic material of HIV, which mutates frequently inside those infected with it, would forever remain inside the vaccine recipient. Gallo insists that a vaccine based on a retrovirus would mutate and eventually cause AIDS, cancer or some other deadly illness.

It could be years before a live-virus AIDS vaccine could be ready for testing in humans.

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