Advances Inject Hope Into Quest for Vaccine

"In the past we maybe inappropriately said we'll judge a vaccine primarily on the basis of being able to prevent infection completely," said NIAID chief Anthony S. Fauci. "Now we're thinking maybe it's enough if you get infection but not disease. Until recently we never considered that."

Increasingly, these more modest goals are coming within reach. Chimpanzees and monkeys inoculated with experimental vaccines and then challenged with big doses of HIV (or SIV, the monkey equivalent of HIV) have in several cases been able to block the initial viremia, with virus levels dropping quickly to near zero -- although in some cases infection reappears later, evidence that the virus was simply suppressed for a time.

It would be unethical, of course, to expose human volunteers to HIV deliberately. But in recent tests in volunteers, several different vaccines have elicited responses similar to those seen in animals.

In early human tests of the canarypox vaccine given to Lynch, for example, the bird virus and its Trojan horse cache of HIV genes stimulated a potent blend of both killer T-cells and antibodies. Moreover, researchers found they could boost HIV antibody levels in these volunteers even higher by following up with additional shots of gp120, a laboratory-grown protein identical to one found on the outer envelope of HIV.

In an especially inspiring result reported in May, killer T-cells induced by the canarypox vaccine fought off multiple strains of HIV in test tubes -- including strains from Africa and Asia -- even though the vaccine is made from genes taken from a single North American strain of HIV. That provided the first solid hope that researchers may not have to develop separate vaccines for each of the eight major known strains of HIV that infect people in different parts of the world.

In June, the NIH gave the nod to try this "prime-boost" approach -- modified canarypox followed by gp120 -- in a phase II test of 420 people in 14 cities, including St. Louis. If the vaccine still looks safe and stimulates reasonable numbers of antibodies and T-cells in these people, then it may become the first AIDS vaccine ever to be promoted to a full-scale testing to determine its effectiveness.

That trial would be unprecedented in size, scope and significance, involving 5,000 to 10,000 HIV-negative men and women deemed at high risk of getting AIDS, and would go on for several years. Out of such a trial, the world's first marketable AIDS vaccine would emerge.

The canarypox vaccine, made by Pasteur-Merieux/ Connaught, is only the second AIDS vaccine to have made it even to phase II testing in the United States. The other, a genetically engineered version of gp120 given alone, gave mixed results a few years ago that some interpreted as hopeful and others as too equivocal to justify the expense of a phase III study. In June 1994, citing gp120's inability to stimulate T-cells, the failure of gp120 antibodies to neutralize some strains of HIV, and a lack of support from the gay community -- where the vaccine would be tested -- NIAID director Fauci decided against large-scale testing.

It was a decision that haunts Fauci to this day -- not because he thinks it was wrong, but because he will never know whether he was right. Others, like Belshe, are more certain.

"It was the worst decision the NIH ever made in terms of vaccine development," Belshe said. "We knew it was safe. We knew it induced antibodies. I have no idea how well it might have worked, but now we never will know because they pushed a negative decision too fast."

Moreover, Belshe argues, that controversial decision had repercussions beyond gp120 that can still be felt today. "It showed uncertain support from the government. It said to manufacturers, 'We're not going to back this effort.' "

Corporate reticence has persisted ever since, according to a December 1996 analysis by the nonprofit AIDS Vaccine Advocacy Coalition (AVAC). "Of the five leading global vaccine manufacturers, only two (Pasteur-Merieux-Connaught and Chiron) have broad-based HIV vaccine programs that are pursuing a number of approaches," the group found.