A collaborative of Dartmouth’s Geisel School of Medicine, Muhimbili University of Health and Allied Sciences in Tanzania, and Tokyo Medical and Dental University received $1.4 million from Japan’s Global Health Innovative Technology Fund (GHIT) to conduct a joint randomized clinical trial in Tanzania aimed at reducing the transmission of tuberculosis (TB). The trial will evaluate the safety and efficacy of DAR-901, a booster TB vaccine, in adolescents.
“We’ve been working on this since the 1990s, and DAR-901 remains the only new vaccine for TB in development that has shown to be effective in humans,” says Ford von Reyn, MD, a professor of medicine at Geisel who led the development of the vaccine. “We are very enthusiastic about moving forward with DAR-901 because the World Health Organization has set a target date of 2035 for global elimination of TB, and modeling indicates that will be possible only if there is a new and better TB vaccine—so we are fortunate to be working on this.”
Modeled after and run in coordination with the Bill & Melinda Gates Foundation’s Grand Challenge initiative, GHIT’s Grand Challenges Targeted Research Platform initiative funds early-phase research and development approaches to fighting infectious disease.
Tuberculosis is a major cause of death worldwide. In 2013, there were an estimated 9 million new cases of TB and 1.5 million deaths from the airborne disease, which is both preventable and curable. TB is also the leading cause of death among people living with HIV. Von Reyn’s Dartmouth team has been focused on research to combat TB since his tenure with the World Health Organization’s AIDS program in 1987.
The current vaccine developed in 1928, Bacillus Calmette-Guérin (BCG), is a live vaccine typically administered at birth, but does not offer lifelong immunity—it is effective for only 15 years and subsequent shots of the vaccine do not create a boost. DAR-910 is designed to boost and prolong BCG’s protection. DAR-901 is an inactive form of a whole cell mycobacterium derived from a non-TB organism that is closely related to TB.
An earlier randomized, controlled clinical trial conducted by von Reyn in Tanzania, showed that the inactivated vaccine booster reduced the rate of TB among HIV infected adults. During the new DAR-901 Prevention of Infection in Adolescents Trial (DAR-PIA), DAR-901 will be administered to a total of 650, 13-15-year-old participants who received BCG at birth. If DAR-901 proves to be safe and effective in reducing TB infection in adolescents, von Reyn says a subsequent multi-site clinical trial will target the general population of people living in TB endemic countries.
“It is impressive what Ford and his team have been able to accomplish,” says Interim Dean Duane Compton. “The burden of TB worldwide is huge and Ford has developed the most promising vaccine to combat this deadly disease."
The DAR-PIA trial represents a new paradigm in TB vaccine trials. Most TB vaccine efficacy trials are designed to determine protection against full-blown symptomatic TB disease. According to von Reyn, the DAR-PIA trial is designed to prevent newly acquired TB infection, a condition that is clinically silent but represents the first stage in eventual progress to symptomatic TB disease. A blood test known as an IGRA will be used to detect infection. In TB endemic countries there are 10 cases of TB infection for every one case of TB disease, so a trial based on preventing infection can be conducted with fewer subjects and with a shorter period of follow-up than a trial based on preventing disease. One other prevention of TB infection trial is currently underway in South Africa.
Quick to point out that changing the course of the TB epidemic is a team effort, von Reyn notes, “We’ve worked with a team from Dartmouth and various collaborators in Boston and Tanzania over the years, so this is not a grant awarded to one person—it’s for a vaccine development team, and we are honored to be able to move on to the next phase with our colleagues.”
Lisa Adams, MD, an associate professor of medicine at Geisel, and one of von Reyn’s collaborators says, “Having devoted my career to TB control, I can attest that a new, safe, and effective TB vaccine will be a game-changer in our efforts to eliminate TB globally.”
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ABOUT THE GEISEL SCHOOL OF MEDICINE AT DARTMOUTH – Founded in 1797, the Geisel School of Medicine at Dartmouth strives to improve the lives of the communities it serves through excellence in learning, discovery, and healing. The Geisel School of Medicine is renowned for its leadership in medical education, health care policy and delivery science, biomedical research, global health, and in creating innovations that improve lives worldwide. As one of America’s leading medical schools, Dartmouth’s Geisel School of Medicine is committed to training new generations of diverse leaders who will help solve our most vexing challenges in health care.
ABOUT GHIT: The first of its kind in Japan, the GHIT Fund is a public-private partnership between seven Japanese pharmaceutical companies, the Japanese Government, the Bill & Melinda Gates Foundation, the Wellcome Trust, and UNDP. Launched in April 2013 with an initial commitment of more than US$100 million, the organization taps Japanese research and development (R&D) to fight neglected diseases. The GHIT Fund invests and manages a portfolio of development partnerships aimed at neglected diseases that afflict the world’s poorest people. GHIT mobilizes Japanese pharmaceutical companies and academic and research organizations to engage in the effort to get new medicines and vaccines to people who need them most, with Japan quickly becoming a game-changer in global health.
For more information, please visit http://www.ghitfund.org