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HIV Vaccines: Optimism and Frustration
by Bob Roehr

This article shared 1048 times since Wed May 23, 2001
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The search for a vaccine against HIV got a huge boost when President Bill Clinton committed to developing one by 2007 in a speech at Morgan State University in 1997. Few doubt the need. An estimated 15,000 new infections a day occur throughout the world, most in nations too poor to afford therapy. Prevention is key, and a vaccine is the ideal capstone to prevention activities.

The AIDS Vaccine Advocacy Coalition ( AVAC ) has used the May 18 anniversary of Clinton's speech to issue an annual report on progress made toward the goal of an AIDS vaccine. This year's edition, "6 Years and Counting" [ down ] , offers an upbeat assessment of momentum gained over the last year.

But huge problems remain and major questions seem no closer to being answered than they were at the start of the epidemic. That became apparent in a May 16 phone news conference that AVAC had with reporters.

On the plus side, AVAC executive director Rose McCullough counted "several new and interesting studies in monkeys of vaccine that have demonstrated good levels of protection;" increased participation by industry in HIV vaccine research by many whom had earlier shunned such activity; continued and increased research funded by the National Institutes of Health ( NIH ) ; and many more candidate vaccines that are about ready to enter human trials.

She said, "The promise of that progress requires a new level of political and scientific leadership." That includes continued increased funding of research; passage of tax credits to draw industry's commitment; and expansion of global capacity to test vaccines in the populations most affected. It will require leadership from the United States.


But as everybody readily admits, vaccine trials in monkeys are not the same as trials in humans. At the level of basic science, monkeys do not become infected with HIV so researchers use a simian virus ( SIV ) , somewhat akin to HIV. Most monkey trials vaccinate the animal, wait long enough for protection to develop, then expose it to a single dose of SIV high enough to infect 100 percent of unprotected animals. Six months later, if the animal does not develop infection, the vaccine is considered a success.

This may be good science, but it does not reflect the way humans are likely to be exposed to HIV though continuous sexual activity. Nor does it reflect the fact that levels of protection with many vaccines decline over time. There is some evidence to suggest that the protection from HIV may fall especially quickly, perhaps in just a few months.

Researchers followed a small group of prostitutes in Kenya who were continuously exposed to HIV yet did not become infected with the virus. These few examples offered hope that it was possible to develop a natural immune protection from infection, and hence a vaccine. But many of these women developed HIV when they took a break from the trade and then went back to it after a few months. This suggests that they needed constant exposure to HIV to maintain their natural defenses and that those defenses fall rather quickly once exposure is reduced.

Many people see as a hopeful sign the fact that about a dozen candidate vaccines are nearly ready for human trials. The vaccines cover a huge range of approaches, use various different parts of the HIV genome, boosting agents, and inoculation strategies to try to elicit immune protection.

But the very diversity of approaches is an indication of how little we know about "the correlates of protection," of what is the critical immune response that people need in order to fight off HIV infection. "We don't have that information yet," said Susan Buchbinder during the conference call. She is a vaccine researcher at the University of California San Francisco. She hopes that some of that information will come from initial large-scale trials "to help guide future efforts."

Another open question is whether a single vaccine can be developed that is effective against all of the strains of HIV. Researchers have identified a handful of major strains of the virus, each with multiple variations.

Influenza ( the common flu ) , like HIV, is another highly divergent and rapidly mutating virus. New variations of the flu vaccine have to be prepared and populations inoculated on an annual basis to afford some protection.


"Sterilizing immunity" represents the optimum goal of a vaccine. It means that a person will completely resist exposure to a virus and no trace of it will be left in their body. Most researchers believe that an HIV vaccine will not protect 100 percent of those who receive it, at least not initially and perhaps ever.

While some people may be protected, the initial vaccines likely will prime the immune system so that any infection is a kinder, gentler version of HIV disease that develops more slowly and can be better controlled.

"You could argue that in some parts of the world it would be better to slow disease progression than not to do anything at all," said Buchbinder. It may be that countries and risk groups make different decisions on about when it makes sense to use a vaccine with limited effectiveness.

Complicating the matter further is the issue of "therapeutic vaccines." Can a vaccine or another agent that is given after a person becomes infected, help boost the immune response to better control HIV infection? The answer seems to be yes. And that makes the risk/benefit of a vaccine that offers only limited protection even more difficult to evaluate.

The practical matter is that it takes a minimum of four years to complete early phase I and II trials that test for safety and immune response in small groups of people. Phase III trials, the larger population studies that test vaccines under real world conditions to evaluate their protective power, take even longer.

Only three products have even entered human trials, and expectations for them are muted. As David Gilden, with the American Foundation for AIDS Research ( amfAR ) , concluded, "It is going to take at least a decade to begin to see if a vaccine is partially effective, at best."

This article shared 1048 times since Wed May 23, 2001
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