Disclosing results of a clinical trial, researchers at Dartmouth Medical School (DMS) have shown that a new vaccine against tuberculosis, Mycobacterium vaccae (MV), is effective in preventing tuberculosis in people with HIV infection. The DarDar Health Study, named for Dartmouth and Dar es Salaam, Tanzania, found that MV immunization reduced the rate of definite tuberculosis by 39 percent among 2,000 HIV-infected patients in Tanzania.
“Since development of a new vaccine against tuberculosis is a major international health priority, especially for patients with HIV infection, we and our Tanzanian collaborators are very encouraged by the results of the DarDar Study,” said Principal Investigator Dr. Ford von Reyn.
The 7-year, randomised, placebo-controlled trial was conducted in Tanzania with collaborators at the Muhimbili University of Health and Allied Sciences (MUHAS) in Dar es Salaam, and was supported by a grant from the National Institutes of Health (NIH) in the United States. “The study confirms that University institutions from the northern and southern hemispheres can establish partnerships to perform quality clinical research work with global importance. The results of the study are not only good news for people living in regions with high infection rates of HIV and tuberculosis but has also contributed to capacity building in performing TB vaccine trials among HIV infected persons in Tanzania,” said Dr. Kisali Pallangyo, the senior collaborator at MUHAS.
Since newly-infected HIV patients risk contracting TB almost immediately, Dartmouth investigators are targeting a strategy for immunization with MV before patients need to start taking antiretroviral drugs.
In Phase-I human studies, the researchers demonstrated that a multiple-dose series of MV was safe in both healthy subjects and patients with HIV infection.
The group then conducted Phase-II studies in larger groups of adults in Zambia and in Finland. In the Zambian trial, it was found that MV boosted immune responses against tuberculosis that had first been primed in childhood with the current TB vaccine, BCG.
Then they conducted the large Phase-III efficacy trial among HIV-infected patients with prior BCG immunization in Tanzania.
Von Reyn, a Professor in the Department of Medicine at DMS, described the DarDar trial as “a significant milestone” - the first to demonstrate that any type of vaccine can prevent an infectious complication of HIV in adults.
He added that the next steps are to improve the manufacturing methods to support the production of the larger quantities of the TB vaccine needed for further studies and subsequent clinical use. Development work on manufacturing will be conducted by the Aeras Global TB Vaccine Foundation in Rockville, Maryland, in conjunction with the London-based manufacturer, Immodulon Therapeutics.
“Aeras’ goal is to speed the development and distribution of new TB vaccines for those who need them most. We are pleased that our internal manufacturing capacity can assist in the further development of this TB vaccine,” said Dr. Jerald C. Sadoff.
The vaccine is a type known as an inactivated, whole-cell mycobacterial vaccine and is expected to be economical to produce and distribute, said von Reyn.
The study appears in the latest online issue of the journal AIDS and it will be published in the March print issue of AIDS.