Tuberculosis (TB) is a major cause of death worldwide, and the number one cause of death in persons with HIV infection. Drug-resistant TB, an increasingly global epidemic, requires treatment with toxic and expensive drugs.
The most effective strategy for the control of TB is, of course, prevention. The current vaccine against TB, known as BCG, is given at birth in most countries with high burdens of TB. Though effective for the first few years of life, BCG does not offer complete or durable protection against TB, and a second dose (booster) is not effective. Development of an improved TB vaccine for the world is a major international health priority.
More than 30 new TB vaccines have entered development over the past twenty years. Some have failed; others are only in early stages of development. The only new TB vaccine to have shown efficacy in humans is the TB vaccine being developed by Dartmouth investigators. The DarDar Trial, a 7-year 2,000-subject rigorously designed trial conducted in Tanzania and sponsored by the National Institutes of Health showed that this vaccine, SRL 172, was safe and effective in persons with HIV infection. A new, scalable method of manufacture has been developed by Aeras with funding from Dartmouth and the vaccine is now designated DAR-901. Dartmouth investigators are soliciting support to continue expeditious development.
A whole cell mycobacterial vaccine to be given as a booster to adults
Heat-killed for safety
Derived from a non-TB organism closely related to TB
Worldwide license to Dartmouth for TB prevention (Immodulon, London)
Ford von Reyn MD, Principal Investigator, is Professor of Medicine at Geisel School of Medicine and the 2013 recipient of the Lifetime Achievement Award from the International Union against Tuberculosis
Tim Lahey MD, MMSc, Investigator, is Associate Professor of Medicine at Geisel and one of two 2004 national recipients of the Infectious Disease Society of America Young Investigator Award
Robert D Arbeit MD, consultant, is former Associate Chief of Staff for Research at the Boston VA and has 12 years of experience in industry drug development
C. Robert Horsburgh MD, consultant, is Chairman, Department of Epidemiology, Boston University School of Public Health and has been a leader of numerous national and international TB treatment trials
A non-profit institution based in Rockville MD with a mission to develop a new, effective and affordable TB vaccine for the developing world (www.aeras.org)
Data-driven, impartial decisions on supporting TB vaccine development made thru its expert Vaccine Advisory Committee
Funded principally by the Bill and Melinda Gates Foundation for TB vaccine development
7 vaccines in development portfolio, DAR-901 added in March 2014
Staff of 160 covering all aspects of vaccine research, development and manufacturing, annual budget of $55 million, includes TB vaccine manufacturing facility
SRL 172 is the only new TB vaccine to have progressed to Phase III showing efficacy in humans
DAR-901 represents a new scalable manufacturing method for SRL 172 developed by Aeras to permit manufacture in commercial quantities at reasonable cost.
DAR-901 represents an entire bacterial organism and includes thousands of different antigens to stimulate a broad immune response. In contrast, two other recent subunit candidate vaccines each presented only a single antigen, stimulated a narrow response, and have failed in clinical trials.
Millions of doses annually for all countries where TB remains endemic including China, India, Africa and most of the remaining developing world
Estimated annual revenues of $100 million
Development is largely philanthropic
In 2012, Dartmouth, under the leadership of President Jim Kim, CFO Steve Kadish and Geisel Dean Chip Souba, provided $1.2 million to support the initial work for DAR-901. These funds enabled development of the new manufacturing method, completion of animal studies, filing of an IND with FDA on January 9, 2014, and acceptance of the IND on February 10, 2014.
DAR-901 was added to the Aeras Vaccine Portfolio on March 19, 2014. With joint sponsorship Dartmouth and Aeras initiated a 77-subject, 14-month Phase I trial with DAR-901 at Dartmouth (New Hampshire, USA) in April 2014.
Successful completion of the Phase I trial will make DAR-901 attractive to large pharmaceutical companies.
A pivotal Phase III could then be conducted in 3 years with potential world-wide licensure in 5 years
Vaccine development always entails risk. But, the 15 year experience with SRL 172, including safety and efficacy in humans, provides DAR-901 a stronger foundation and higher likelihood of success than any other TB vaccine in development
The extensive competition for resources and support makes it critical to maintain the momentum that has been generated by the initial funding from Dartmouth.
An effective new TB vaccine would, literally, save millions of lives world-wide and is essential for achieving the Millenium Development Goal of eliminating TB globally by 2050
Success would bring worldwide recognition for Dartmouth College and Geisel School of Medicine
An additional $300,000 is needed to fund the last 6 months of the Phase I trial. This will ensure that it provides all of the data required to move directly to a Phase III trial in Tanzania
Full information and on-site presentations are available from Dr. Ford von Reyn
C. Fordham von Reyn MD
Director, DarDar International Programs
Professor of Medicine
Infectious Disease and International Health
Dartmouth-Hitchcock Medical Center
Hanover, NH 03756
Reference: von Reyn CF et al. Prevention of tuberculosis in BCG-primed, HIV-infected adults boosted with an inactivated whole-cell mycobacterial vaccine. AIDS 2010; 24:675-85