A clinical trial conducted by Dartmouth Medical School researchers has shown a new vaccine to be effective in preventing tuberculosis in HIV-positive populations. Investigators from the DARDAR Health Study determined that the vaccine reduced the rate of TB infection by 39 percent in patients infected with HIV, compared to those who received no vaccine, according to DMS professor and principal investigator Fordham von Reyn.
The DARDAR Health Study a collaboration between DMS and the Muhimbili University of Health and Allied Sciences in Dar es Salaam, Tanzania conducted the seven-year, double-blind trial among 2,000 HIV-positive individuals, according to von Reyn.
Many countries with high rates of TB administer the Bacille Calmette-Guerin vaccine, a standard TB vaccine, routinely at birth. The immunity provided by the BCG vaccine does not last into adulthood, leaving HIV-positive adults susceptible to TB, von Reyn said.
"TB is the leading cause of death from HIV in the developing world," he said.
Only those in an early stage of HIV infection who did not have active TB, were not pregnant and had received the BCG vaccine at birth were eligible for the study. Half of the participants received a placebo and the other half received the vaccine, von Reyn said.
The clinical trial showed that the group receiving the vaccine had a rate of TB infection that was 39 percent lower than the group receiving the placebo, according to von Reyn.
The new vaccine uses a strain of Mycobacterium vaccae, a bacterium similar to the pathogen that causes TB. Because the MV vaccine uses a heat-killed pathogen, it carries no risk of causing an infection, von Reyn said.
"Our particular focus was to develop a vaccine that would be safe and effective in AIDS patients," von Reyn said. "Live versions are much more difficult to prove safe."
The DARDAR study proved that the MV vaccine boosts immunity in adults who receive the BCG in childhood, according to DMS professor Lisa Adams, a co-investigator in the study and the director of Dartmouth's Global Health Initiative.
"This is a milestone in TB vaccine development for people with HIV," von Reyn said. "If even 50 percent of people in Tanzania were immunized, we could prevent 3,000 cases of TB a year."
This vaccine will have the greatest impact in countries with high rates of HIV infection, but it also has a wide range of applicability, DMS professor and co-investigator Richard Waddell said.
"In theory, this could be used in any country where TB is endemic and people are immunized with BCG," Waddell said.
Von Reyn stressed that the vaccine is relatively inexpensive to manufacture, which may have implications for the field of vaccine development.
"The trial shows that there are ways to manage infection in a developing country in an inexpensive way," Waddell said.
Adams said she believes that the collaborative nature of the study was essential to its success, noting the work of the Tanzanian colleagues in particular.
"We couldn't have picked a better group to work with," she said. "This was a true partnership, which made it such a great experience."
The collaborative effort of the DARDAR Health Study could serve as a model for future work in this field, according to Robert Arbeit, a co-investigator and adjunct professor at Tufts University School of Medicine.
"This was a four-way collaboration between the [National Institutes of Health], academics at Dartmouth, people on the ground in Tanzania and the pharmaceutical company that created the vaccine," Arbeit said.
Arbeit stressed the importance of a joint effort in tackling diseases like TB.
"All these [contributors] are needed if we are going to develop these new drugs in places where it may not be economically suitable for pharmaceutical companies to do it alone," he said.
The success of the study proves that it is possible to prevent other infectious diseases in HIV patients, said C. Robert Horsburgh, a co-investigator and chairman of epidemiology at Boston University School of Public Health.
Horsburgh said that their findings could encourage drug developers to devote more resources to TB and HIV research.
Investigators from the DARDAR study will work with the Aeras Global TB Vaccine Foundation to develop another version of the vaccine, as the vaccine in its current form is not suitable for mass-production, Adams said. As a result, it may be several years before the vaccine can be widely administered, von Reyn said.
The team now intends to administer the vaccine in Tanzania to participants in the study who received the placebo, Adams said.
