Vaccine against virus that causes AIDS ‘clearly remains beyond our grasp,’ researcher says during HIV ‘town hall’ meeting this week
A vaccine against the virus that causes AIDS "clearly remains beyond our grasp," according to Warner Greene, co-chair of the HIV Vaccine Summit, despite the "hundreds and hundreds of millions of dollars" spent to find one.
Greene, a researcher at the University of California San Francisco, made his dreary pronouncement at the one-day town hall meeting in Bethesda, Md., on Tuesday, March 25.
Anthony Fauci with the National Institutes of Health said researchers had "asked the question: Do we need to make an adjustment in the balance between discovery and development" in HIV vaccine research. The answer, he said, "is an overwhelming yes."
The re-evaluation process comes after the failure last fall of a second vaccine candidate. While few expected the vaccine to protect against infection, they hoped that it would help train the immune system to better fight HIV and result in slower progression to disease for those who became infected.
But the shocking finding was that those who received the vaccine appeared to be slightly more likely to become infected with the virus than those who received a placebo. The trial was stopped and researchers are still conducting analysis to try to understand why.
A consistent theme throughout this week’s meeting was the need for innovation and new ideas. Many speakers urged increased spending on basic research and a broad definition of what might contribute to vaccine research.
That includes a better understanding of the steps the virus takes in establishing infection, how elite and slow progressors are better able to control the virus, and better use of the monkey model to guide vaccine development.
University of Alabama Birmingham researcher Beatrice Hahn said that continuing down the current path toward a "vaccine product" is not productive, adding, "New discovery cannot always be two steps removed from a final product."
Rafi Ahmed from the Emory University Vaccine center said, "Vaccine concepts that test only one arm of the immune system are doomed to failure," arguing that because "T cells cannot control infection on their own," a vaccine must also stimulate broadly cross-reactive neutralizing antibodies produced by B cells.
Vaccines that have gone into clinical trials so far have tried only to stimulate T cell protection. But T cells take hours or days to respond to an infection, while the innate immune response of B cells is present in the mucosal tissue where the virus first enters the body through sexual contact, Ahmed pointed out.
Seth Berkley, president of the International AIDS Vaccine Initiative, said there are crucial differences between trials that are designed to answer scientific questions and those designed to gain FDA approval. The later trials generally are larger.
Berkley said a shift away from developing a vaccine for immediate use will mean a change in design and perhaps a reduction in cost of those trials.
Meeting participants were careful to affirm the dynamic interplay of clinical trials and basic research, with key discoveries made through both processes that have helped to shape further research in both areas.
Scripps Research Institute immunologist Dennis Burton concluded, "We need to change our mindset. We need to move from product development to scientific investigation. … I think there is a growing consensus that one needs to move funds from development to discovery."
Follow the money
Fauci controls an annual AIDS research budget of about $1.5 billion, about a third of which is devoted to vaccines. However, NIH has received little or no increase in funding over the past five years, resulting in a 12.3 percent decline in purchasing power.
Fauci made the case for increased funding but acknowledged the political reality is likely to doom that possibility. That means shifting resources within existing programs, he said.
Later in the day, Project Inform’s Martin Delaney noted that all of the discussion had been about the "easy" questions of what areas need increased funding. He urged them to take up the more difficult task of where "the less money" is going to come from.
No one took up his challenge.
Fauci repeated several times throughout the day that "everything is on the table" in terms of shifting resources. When pressed as to whether some of that might come from treatment trials conducted in the US, he danced around the issue.
"It is entirely reasonable to believe that over time, there will be the need for different emphasis on different things," Fauci said.
This article appeared in the Dallas Voice print edition March 28, 2008
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