This is the second story in a five-part series on Duke's 20 years of research and social work against AIDS.
As nothing more than a tiny ball of protein filled with strands of DNA, the AIDS virus--1/80 the size of a red blood cell and lacking the most basic elements of life--has surprisingly managed to outsmart some of the greatest medical minds of this generation.
Since 1987, more than 30 HIV vaccines have passed the test tube stage, but none have shown the ability to stop the disease in patients. Yet the pessimism engendered from this lack of progress has ebbed in recent years, and some researchers are beginning to say that they may be able to win the fight against AIDS after all.
In 2000, Duke University Medical Center became a central player in AIDS vaccine research. A $27 million grant from the National Institutes of Health established the Medical Center as the base for the national HIV Vaccine Trials Network and handed Duke the responsibility for testing and coordinating searches for the most promising federally-funded vaccines of the future.
"Duke certainly ranks among the top 10 institutions in the country for what has happened so far in AIDS therapeutics," said Dr. Sandy Williams, School of Medicine dean. "A vaccine remains elusive, but chances get better and better."
The search for an HIV vaccine is requiring some radical new thinking from immunologists. "Immunity to HIV is complex and no one understands it well," said Dr. John Bartlett, director of the Duke AIDS Research and Treatment Center.
Most viral vaccines--such as for polio and measles--essentially work by stimulating the body's immune response to a disease in advance. Thus, when the virus finally invades the body, antibodies adept at preventing its entry into cells--a necessary step for viruses to replicate--are already swarming through the blood stream.
HIV, however, has found a way around this strategy.
The traditional method of provoking the initial immune response is to inject a weakened form of the virus, but researchers fear that HIV is so resilient and adaptable that the vaccine might quickly mutate into a full-blown infection.
In addition, HIV attacks the helper T-cells--responsible for coordinating immune system response--and leaves antibodies ineffective and directionless.
"The AIDS crisis requires an entirely new strategy," said Dr. Charles Hicks, associate director of DART, who is studying the mechanisms of the disease shortly after it first invades the body.
Barton Haynes, chair of medicine at the Medical Center and a long-time AIDS researcher, outlined five broad challenges that must be overcome to develop an AIDS vaccine. Three of them--protecting helper T-cells, provoking white blood cells that can kill already-infected cells and providing a protein for long-lasting immunity--have been solved, he said.
The Medical Center is currently pioneering a solution to the fourth problem--provoking an immune response without using a weakened form of HIV--by strategically combining short pieces of the virus' harmless protein coat.
However, the greatest stumbling block for this approach is the fifth problem--the broad genetic variability and rapid mutation of the AIDS virus.
"HIV is the most rapidly evolving and highly variable agent known in the history of medicine," Haynes said. "This produces an extraordinarily difficult problem for researchers."
Feng Gao, an associate research professor at Duke's Human Vaccine Institute, who is confronting the variability problem, explained that the most widespread HIV group contains 10 widely divergent subtypes. An effective vaccine must be able to simultaneously combat each of these subtypes and head off any new genetic mutations AIDS develops.
The Medical Center is collaborating with Los Alamos National Laboratory on a method that analyzes the different strains of HIV and strategically engineers the protein coat--called a consensus sequence--that represents a middle ground between the original strains.
"You can start with a 30 percent difference between strains A and B, but the consensus sequence difference from each is now only 15 percent," Gao said. "This is one of the best ways to tackle the genetic variation."
This year marks the half-way point of former president Bill Clinton's 1997 challenge to the medical community to develop an HIV vaccine within a decade. Although unsteady progress marked the field after the virus' discovery in 1984, recent advances are seen as encouraging.
"We're making progress. Three of the five problems are solved," Haynes said. "I'm guardedly optimistic that we're going to solve the other two soon."
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