The two-decade search for an AIDS vaccine is in crisis after two field tests of the most promising contender not only did not protect people from the virus but may actually have put them at increased risk of becoming infected.

The results of the trials, which enrolled volunteers on four continents, have spurred intense scientific inquiry and unprecedented soul-searching as researchers try to make sense of what happened and assess whether they should have seen it coming.

Both field tests were halted last September, and seven other trials of similarly designed AIDS vaccines have either been stopped or put off indefinitely. Some may be modified and others canceled outright.

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Numerous experts are questioning both the scientific premises and the overall strategy of the nearly $500 million in AIDS vaccine research funded annually by the U.S. government.

"This is on the same level of catastrophe as the Challenger disaster" that destroyed a NASA space shuttle, said Robert Gallo, co-discoverer of the human immunodeficiency virus (HIV), which causes AIDS, and head of the Institute for Human Virology in Baltimore.

The recently closed studies, STEP and Phambili, used the same vaccine -- made from a common respiratory virus called adenovirus type 5 that had been crippled and then loaded with fragments of HIV. Both studies were halted when it became clear the STEP study was futile and possibly harmful.

The results of the Phambili vaccine trial, which was conducted in South Africa, were revealed last month and only worsened the gloom. Although the number of new HIV infections in that study was far smaller than in STEP -- and too few to draw firm conclusions from -- those results, too, hinted at a trend toward harm among vaccine recipients.

Many researchers are questioning the scientific premises on which all those studies were based and are wondering, along with AIDS activists, what effect this near-worst-case scenario might have on tests of future vaccines.

The working hypothesis for what went wrong is that the vaccine somehow primed the immune system to be more susceptible to HIV infection -- a scenario neither foreseen nor suggested by previous studies.

The National Institutes of Health, which funded the STEP and Phambili trials, is convening a meeting next week to reassess its AIDS vaccine program. But some respected scientists have already reached a verdict.

"None of the products currently in the pipeline has any reasonable chance of being effective in field trials," Ronald C. Desrosiers, a molecular geneticist at Harvard University, declared last month at an AIDS conference in Boston. "We simply do not know at the present time how to design a vaccine that will be effective against HIV."

He told a rapt audience that he has reluctantly concluded that the NIH has "lost its way in the vaccine arena" and that he thinks it should redirect its AIDS vaccine funds to basic research and away from human trials.

In this fiscal year, the NIH's budget for AIDS vaccine research is $497 million. The STEP and Phambili trials were each expected to cost about $32 million. Pharmaceutical giant Merck & Co. has spent an undisclosed amount developing the vaccine and helping to manage the studies.

"We can't afford to have any more trials like this," said Mark Harrington, head of the activist Treatment Action Group and a longtime observer of AIDS research. "We have to stop and reassess and recommit to basic science, or people will begin to lose faith."

At the moment, only two things are certain.

The first is that the vaccine, developed by Merck, could not have caused HIV infection because it contains only three proteins from HIV, not the entire virus. The second is that there are no obvious villains.

"I do not think that what happened in this trial is an example of scientists blindly rushing into dangerous things," said John P. Moore, an AIDS virologist at Weill Cornell Medical College, who has criticized vaccine trials he considered futile. "In the general HIV-research community, I didn't know anyone who said this was going to happen."

Both trials recruited people who were at high risk of HIV infection through sexual activity. The STEP subjects included many male homosexuals; the Phambili volunteers were male and female heterosexuals. Half the people in each trial were randomly assigned to get three shots of vaccine, and half to get three shots of a harmless liquid containing no adenovirus or HIV proteins.

Each trial was to have 3,000 participants. STEP had finished enrolling subjects in North and South America, the Caribbean and Australia. Phambili (which means "moving forward" in the Xhosa language of South Africa) had signed up 801 by the time it was shut down.

While scientists hoped the Merck vaccine might prevent some infections, its chief purpose was to stimulate "cell-mediated" immunity to produce a less severe illness. Specifically, the vaccine was expected to lower the "viral load" of HIV in the bloodstream, which in turn would both prolong survival and lessen the chance the person would infect others.

Many experts are questioning the wisdom of that strategy, even if it had worked perfectly. Urging millions of people to take an AIDS vaccine that probably would not protect them from the virus, they say, would be a hard and confusing task, even in places where the epidemic still rages.

For the moment, that is an academic question. The vaccine failed to achieve any of its goals.

In both studies, people who got vaccine were more likely -- not less -- to become infected, with trends suggesting roughly a twofold risk. In the STEP study, which has many more cases to evaluate, nearly all that added risk was in people who had high levels of antibodies to adenovirus type 5 before they got their first shot -- evidence they had been previously infected with that strain. Uncircumcised men in that group had the highest risk.

So how could this have happened?

The leading theory is that activation of the immune system, a cascade of events that occurs naturally when a person is infected with a virus or bacterium or gets a vaccine against one of them, in some way increased the risk of HIV infection.

Activation causes cells called CD4 T-lymphocytes (among many other things) to proliferate. CD4 cells are the targets of choice for HIV. In their activated state, they are coated with molecules called CCR5 co-receptors, which HIV needs to attach itself to a cell.

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