Vaccines work simply by producing antibodies, right? Well, probably not. And this misconception coupled with basic ignorance of how they do work is stalling the urgent quest for an AIDS vaccine, claim leading HIV researchers. They say no one has bothered to find out how highly successful vaccines like polio, measles and hepatitis B actually protect people from disease.
"I'm amazed by the amount of basic science we don't know," Philippe Kourilsky, director of the Paris-based Pasteur Institute, told the meeting: "We've had many successful vaccines over the past decades but we've missed a chance to see how these vaccines work. Each time a vaccine works the scientific community wanders off and leaves it to the public health workers to use it-and fails to invest in the research. If we had done that we would have been in a much better position to tackle the AIDS vaccine problem."
The assumption that successful vaccines work by simply producing antibodies is almost certainly wrong, Neal Nathanson, director of the US Office of AIDS Research, warns. "Hepatitis B vaccine is a good example. It's amazingly effective but no one knows how it works. And what's really interesting is it does work, even though HBV is a persistent infection-like HIV."
The vaccine probably stimulates some protective effect relying on killer T cells. But no one knows how it does it or what exactly the process is-even though the vaccine has been widely used for nearly ten years. It's a similar story for other highly successful vaccines including polio, measles and smallpox, he says. Ruth Ruprecht, a vaccine researcher and professor of medicine at Harvard Medical School, points out it's hard to get funding to research vaccines that already exist. "I always run into prejudice," she told New Scientist. "They say: 'It's old. What good is it?'"
Even if researchers can plug these huge gaps in their basic understanding, they may face another obstacle in their pursuit of an AIDS vaccine. Inducing antibodies against HIV might, in the initial stages of infection, do more harm than good, claims Ron Montelaro of the University of Pittsburgh.
His studies of a HIV-related virus that infects horses, known as the equine infectious anaemia virus, appears to confirm that the antibodies which initially respond to an infection can help spread the viruses around the body. Some vaccines designed to protect horses from infection make them die more quickly than unvaccinated horses, he found.
This process, whereby antibody production helps rather than hinders infectious agents, has been dubbed "enhancement". Montelaro suggests that these early enhancing antibodies actually help pull virus particles into the cells they are trying to infect. "It's an issue people haven't wanted to think about. But we might have to," he says. Jay Levy of the University of California at San Francisco, agrees: "Efforts to avoid these harmful consequences of HIV immunisation must be given a high priority."
Michael Day reports from the Pasteur Institute meeting in Paris.
New Scientist issue: 27th March 2000
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