amfAR Researchers Make Progress Towards an AIDS Vaccine
By Jeffrey Laurence, M.D.
March 7, 2006—Progress in developing an AIDS vaccine has been frustratingly slow, but threee scientists recently funded by amfAR are building on earlier efforts to bring us closer to that goal
A vaccine to prevent HIV is one of the holy grails of HIV/AIDS research, but while clinical trials of experimental AIDS vaccines are being conducted worldwide, these products have shown scant promise in test tubes or animal models. Not only is there currently no vaccine that can protect against HIV infection, but the quest for such a product has no clear path—neither traditional methods nor newer technologies such as genetic engineering have generated safe candidate vaccines that can elicit protective immune responses. The best we can hope for at the moment, and possibly for decades to come, is a vaccine that won’t block an infection per se but might extend the time it takes for AIDS to develop.
Early on, amfAR recognized that radical new approaches were required, and awarded a grant in 1992 to test the concept of “DNA vaccines” to Dr. Stephen Johnston of Southwestern Medical Center in Dallas. Under this approach the genetic material of any disease-causing organism, including HIV, itself serves as the vaccine. DNA vaccines are very cheap to make, don’t require refrigeration, and have no known side effects. The hope was that by mimicking a natural infection, an AIDS DNA vaccine would elicit protective immune responses characteristic of vaccines that are successful against other viruses.
Initial efforts to develop an effective AIDS DNA vaccine seemed promising. Indeed, in the test tube and in monkeys, DNA vaccination provoked rapid killer-T-cell responses, reactions that had not yet been seen with other experimental AIDS vaccines. In 1996 The Economist noted, “If this approach works, it could be a simple way to make cheap, safe, and effective vaccines. So far, the data have been astonishingly good.” Dr. Johnston, whose early grant applications were rejected by federal agencies for being premature, recalled, “amfAR was the only one that would fund DNA vaccination. amfAR was there from the beginning.”
Ten years have elapsed since then—so what has happened? Over the course of the decade, research showed that DNA vaccines by themselves cannot evoke strong enough immune responses to block HIV. And so, recognizing that measles and other virus vaccines are normally administered with a help-mate or “adjuvant” to strengthen immune responses, amfAR-funded scientists set to work to do two things: 1) design a powerful DNA AIDS vaccine adjuvant; and 2) better define what parts of the AIDS virus might make the best vaccine target.
The most recent reports of progress in both arenas come from two articles in the February 2006 issue ofThe Journal of Virology, written by three amfAR-funded scientists. Dr. Richard Kornbluth of the University of California-San Diego found a novel adjuvant in the form of two immune proteins, CD40L and GITRL, which boosted both killer-T-cell and antibody responses to HIV proteins when tested in mice. His group is now testing other proteins in the same family as CD40L and GITRL, hoping to find proteins that generate an even stronger response. In parallel, Drs. Florence Brunel and Rosa Cardoso of the Scripps Research Institute in La Jolla, California, identified the exact regions of HIV that appear to elicit anti-HIV antibodies capable of neutralizing many different strains of HIV. These broad reactions are critical to vaccine design for it would be an insurmountable task to design different vaccines to cover every type of HIV virus circulating in the world.
Many experts believe a vaccine would provide our best chance to stop the HIV/AIDS pandemic. While we are still many years from having such a product available, amfAR-funded researchers continue to make important steps towards this elusive goal.
Jeffrey Laurence, M.D., is amfAR’s senior scientific consultant for programs.