San Franciso Chronicle - Monday, June 4, 2001
Keay Davidson, Chronicle Science Writer

In June 1990, Dr. Wayne Koff was one of the speakers at an AIDS conference in San Francisco. At that time, he ran the AIDS vaccine program at the National Institutes of Health - and he was very excited by recent developments in animal models of AIDS.

So excited, in fact, that he declared at the conference: "We have cracked open the door, and next year we're going to knock it down," suggesting an AIDS vaccine was close at hand.

Eleven years later, recalling that moment, Koff acknowledges with a laugh: "I think I was a little off."

To laypeople, the progress toward an AIDS vaccine may seem excruciatingly slow. In fact, such seemingly pokey progress is typical of the history of medicine.

"The delay in developing a vaccine is telling us that vaccine development remains an empirical science - despite great scientific advances, we still have to try many candidate vaccines and see what works. And in a disease like AIDS, it often takes a long time to figure out what works," said Dr. Abul Abbas of the University of California at San Francisco.

"Remember that tuberculosis is a much older disease, yet we still don't have a vaccine (for TB) that works in all countries and all populations, and the disease is controlled - largely by public health measures - but continues to flare up," Abbas said.

"My personal view is that the delay with developing an AIDS vaccine is not an indication of some fundamental hidden problem, but more the nature of the (immunological) field."

But aside from the intricacies of immunology, the AIDS virus is also one of the more complex, sinister infections in human history.

"The long delay in developing a vaccine only underlines the basic challenge with a virus like HIV," explained AIDS researcher Dr. Jay Levy of UCSF. "First,

when it infects a cell it becomes part of the genetic make-up of the cell. "The second major challenge," Levy said, "is that it can enter a person within an infected cell, and we have no vaccine thus far that can induce the immune system to recognize an infected cell and destroy it."

Koff, who has a doctorate in immunology and virology, is now senior vice president of research and development at the International AIDS Vaccine Initiative in New York City. He cites the many complexities of doing AIDS vaccine research, ranging from the lack of an ideal animal model for the disease to the difficulties of conducting vaccine trials in impoverished countries.

The most advanced vaccine now under development is AIDSVAX, Koff said - a project of VaxGen Inc. of Brisbane, a corporate spin-off of Genentech. Tests of AIDSVAX have continued for three years on 8,000 gay men around the world. A preliminary analysis of the data is scheduled for late this year, Koff said. In the meantime, Koff cautioned, "people shouldn't get their hopes up or down. We do clinical trials to get these answers."

According to the Wall Street Journal, about a half-dozen vaccines are under development by various firms, among them Chiron Corp. of Emeryville. In February, Merck & Co. began safety tests in humans of a prototype AIDS vaccine.

And GlaxoSmithKline Plc of London announced it would begin testing a new AIDS vaccine later this year in humans.

Looking over two decades of the AIDS epidemic, "there has been an immense amount of resources put into this disease, with its horrible impact on public health," said Dr. Ronald Moss, an immunologist and AIDS researcher at Immune Response Corporation of Carlsbad (San Diego County). "Because of that tragedy, we've learned a lot more about the immune system.

"But we are still far from understanding what we may need to know to develop a completely effective AIDS vaccine."

How to reach us

Comments, questions and suggestions for The Chronicle's Science page are welcome. Reach us by e-mail at science@sfchronicle.com, by fax at (415) 896- 1107 or in care of Science Page, San Francisco Chronicle, 901 Mission St., San Francisco, CA 94103.

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E-mail Keay Davidson at kdavidson@sfchronicle.com.

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