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UMass researchers to test new AIDS vaccine
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By Stephen Smith and Scott Allen, Boston Globe Staff, 3/23/2004
University of Massachusetts researchers yesterday announced that they will soon begin human testing of an AIDS vaccine that recognizes several of the virus's disguises, part of a new wave of experimental immunizations intended to outwit the worst infectious disease since the medieval plagues.
The human immunodeficiency virus that causes AIDS has frustrated vaccine researchers for years, largely because its outer coating changes so readily that it evades the body's defenses. The University of Massachusetts vaccine attempts to get around HIV's deceptiveness by targeting five strains of HIV at once.
"We underestimated the complexity of HIV," said Dr. Shan Lu, the UMass Medical School scientist chiefly responsible for developing the new vaccine. "If you don't even understand your enemy and yet you think you can defeat your enemy, that's naive."
The trial in Worcester is one of at least 18 new approaches to AIDS vaccines underwritten by the National Institutes of Health and one of several now going to human testing. The idea, say NIH officials, is to support numerous approaches in hopes of achieving a breakthrough.
But NIH officials say they are under no illusions. Dozens of experimental vaccines have fizzled, including one made by California-based VaxGen, which failed last year after a $200 million clinical trial.
"I'm very optimistic that we will find a safe vaccine that has some usefulness in my lifetime," said Margaret Johnston, the middle-aged director of the vaccine and prevention research program in NIH's AIDS division.
Today, however, she said vaccine research is still waiting for a major innovation to energize research the way that AZT, the first effective AIDS medicine, revolutionized treatment in the mid-1980s.
Millions of lives are at stake in the quest for an effective vaccine. World health officials estimate that 42 million people are infected with HIV and that 3 million died of AIDS last year. Many of the victims, especially in sub-Saharan Africa andAsia, are too poor to afford treatment, making vaccination the best hope for those not yet infected.
"It's an urgent search whether [the results are] disappointing or jubilant," said Dr. Calvin Cohen, research director at the Community Research Initiative of New England. "We know enough to prevent every single exposure. Yet, clearly,we're unable to do that.... Human behavior is human behavior."
The researchers at UMass, working with a Maryland biotechnology company called Advanced BioScience Laboratories, say they have learned from past vaccine attempts that did not give the body's immune system enough weapons to fend off HIV.
"HIV presents itself as a virus with new tactics to get around our immune system," said Dr. Jeff Kennedy, an assistant professor of medicine at UMass who will lead the vaccine trial. "It is one nasty critter, the ultimate terrorist."
Successful vaccines of the past, such as the smallpox and polio immunizations, had used weak or killed versions of the disease-causing microbe to prime the patient's immune system to fend off the disease in the future.
But, because of modern-day safety concerns, researchers couldn't inject patients with the AIDS virus itself, instead settling for proteins from the HIV. Unfortunately, the proteins didn't provoke as strong an immune reaction as the virus itself would.
However, the UMass team found that by using genetic material, DNA, from the virus, they could get a more potent reaction, including antibodies programmed to repel the virus and killer cells, which eliminate cells once they're infected.
Just as important, the researchers wanted the vaccine to expose patients to as many forms of the HIV virus as possible. So they extracted DNA from five distinct strains of HIV, with two types from the United States, two from Africa, and onefrom Thailand to represent the major strains worldwide.
"It may not be the vaccine that covers everywhere in the world, but if you want to cover as broadly as possible, you try to collect samples from as diverse a population as possible," Lu said.
The UMass researchers weren't interested in the entire genetic recipe of the virus.
Instead, they focused on what scientists call the viral envelope, its external coating, which varies between strains.
"One HIV virus wears a fur coat, the other is wearing a rawhide coat, and the other is wearing a sweater," Kennedy explained. "We're going to inject people so their immune system can see the sweater, so they can see the fur coat, sothey can see the rawhide coat."
The bits of DNA from the five strains were married into a single vaccine that would carry no risk of causing HIV because the DNA is so fragmentary. However, scientists hope the vaccine will trick the immune system into mounting a response to the virus in various forms.
Animal tests showed that the DNA vaccine did precisely that. It provoked a response from both arms of the immune system, producing both the disease warriors known as antibodies as well as killer cells, which are designed to destroy infected cells before the virus spreads.
"The idea," Lu said, "is that if you're infected with a virus wearing this same envelope coat, the body's immune response will recognize that and eliminate the virus."
During a six-month period the 36 participants in the trial will be immunized three times with the DNA vaccine. Recipients will also get two inoculations of proteins that are designed to provide a boost to the DNA vaccine.
While confident they have hit upon a strategy that could one day yield a successful vaccine, Lu and Kennedy both sought to dampen expectations that they now have in their syringes the single answer to the HIV vaccine quandary.
"The HIV vaccine that ultimately is going to be developed and is going to be successful is going to be based on a new concept," Kennedy said. "I think this vaccine we are testing is one step toward that."
The UMass trial is one of four vaccine experiments that are just starting human trials with $70 million in NIH funding. Among them is a study just launched by Chiron Corp. in Emeryville, Calif. Its vaccine, given so far to 30 people, deliversthe DNA of the AIDS virus aboard microparticles that immune cells readily absorb.
"We have to cross our fingers and hope things work," said Susan Barnett, Chiron's HIV vaccine project leader. "And we have to learn if they don't."
Scott Allen can be reached by email at allen@globe.com.
People who are not HIV-positive, fairly healthy and are interested in more information about participating in the trial, should call 888-687-5757. Or, they can log on to www.umassmed.edu/cidvr and click on "clinical trials."
© Copyright 2004 Globe Newspaper Company.
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