HUP researchers test HIV vaccine

An experimental technique aims to clear the virus from patients who are already infected. The tests are only preliminary. Researchers at the Hospital of the University of Pennsylvania have launched a trial of an experimental vaccine for HIV-infected individuals. The vaccine is designed to stimulate a sufficient immune system reaction to clear the blood of the virus, said David Weiner, the Pathology professor who developed the vaccine. Traditionally, vaccines are either live -- growing in the body and mimicking real infections -- or dead. Both types precipitate immune system reactions. While the dead vaccines are safer -- there is no risk of infection from the vaccine -- they do not enter the cells. As a result, they do not cause t-cell production -- the body's most powerful immune response. The new vaccine consists of HIV DNA strands that are injected into the body. These strands precipitate production of a dead vaccine inside the cells, causing t-cell production with no danger of infection. According to Rob MacGregor, the director of the trial, the research departs from traditional science in two ways: The first innovation is the use of a DNA-based vaccine. While such vaccines have been successful in animals, this will be the first real test with human subjects, according to Thomas Merigan, Medicine professor at Stanford University Medical Center. Merigan called the use of the DNA vaccine in an HIV trial "very appropriate" because other vaccines have been so unsuccessful. Vaccines are usually preventative making the goal of this trial unusual. "There has never been evidence of the effectiveness of a vaccine for treatment of an infection, rather than prevention," MacGregor said. While he was initially skeptical, MacGregor said there are two key differences between HIV and other viruses that make the possibility of a curative vaccine plausible. First, HIV is a virus of the immune system, and works by incapacitating that system. Thus, a vaccine which helps the immune system could prove decisive in defeating the virus. Second, HIV has a life span measured in years, providing significantly more time for a vaccine to impact on the course of the virus. Earlier trials at HUP, with a slightly different vaccine, succeeded in stimulating an immune response, which MacGregor said confirmed the possibility of a curative vaccine. However, the earlier vaccine did not succeed in impeding the course of the virus. Weiner explained this was partly due to the use of subjects not undergoing drug therapy for HIV. It is now believed that those infected with HIV undergo a complete turnover every day of their CD4 cells -- the immune system cells with "memories" of diseases. This limits the effectiveness of a vaccine because new cells have not been "taught" how to defend against the virus. This trial will use patients currently undergoing drug therapy that has lowered their HIV levels. These patients' CD4 cells have a normal life-span, which will increase the vaccine's effectiveness. The new vaccine also includes two DNA strands not used in the previous trial. Indeed, "there are at least eight other HIV [related] genes," said MacGregor, any of which could potentially be useful in a vaccine. The trial is a preliminary test of the vaccine's safety and capacity to produce a response. It will involve 21 patients in three groups of seven, each group receiving a successively larger dosage if the vaccine is proved safe at the lower dosage. Such trials are mandated by the FDA before any larger scale trials are run to test the vaccine's effectiveness. If the drug is found to be safe, a large scale trial could start as early as next year, MacGregor.