DAR-901

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 prolonged treatment with toxic, expensive drugs. BCG, the only vaccine currently in use for prevention of TB, is very effective for the first few years of life, but loses efficacy after 10-15 years. Booster immunization of adolescents or adults with a repeat dose of live BCG does not increase protection (presumably because the immunity induced by a priming dose of BCG reduces replication of a booster dose). Therefore, development of an effective booster TB vaccine for the world is a major international health priority. Modeling indicates that an effective booster for adolescents and adults will have a greater impact on disease than an improved BCG for infants and is the only strategy that can be expected to meet the global target of tuberculosis elimination by 2035. New rBCG vaccines being developed for infant immunization may benefit from a strategy that includes an inactivated booster vaccine (i.e., a vaccine that does not require replication) for adolescents and adults.

More than 30 new TB vaccines have entered development over the past twenty years. Several have failed; others are have not reached the clinic; a few are in early stages of development. The only new TB vaccine to have shown efficacy in humans in a fully-powered Phase 3 trial is the booster vaccine being developed by investigators at Dartmouth College. 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 SRL172, a inactivated, whole cell vaccine prepared from an environmental mycobacteria, was safe and effective in persons with HIV infection (von Reyn et al AIDS 2010; 24: 675-685).

In 2013, Dartmouth College obtained from Immodulon (London) an exclusive, transferable, worldwide license for the seed strain of SRL 172 for TB prevention. A new, scalable method of manufacture was developed by Aeras (Rockville, MD) and an initial batch of GMP vaccine prepared. The vaccine product, now designated DAR-901, is the most advanced and promising candidate in the global portfolio. Pre-clinical studies complete include tuberculosis challenge study indicating DAR-901 is superior to BCG booster (Lahey et al, PLoS One, 2016).

What is DAR-901?

  • A whole cell mycobacterial vaccine to be given as a booster to adolescents and adults who received BCG at birth
  • Heat-killed for safety
  • Derived from a non-tuberculous mycobacterium related to TB

 

Who are the members of the development team?

  • 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, is former Associate Chief of Staff for Research at the Boston VA and has 15 years of experience in industry drug development
  • C. Robert Horsburgh MD, Professor, Department of Epidemiology, Boston University School of Public Health and a leader of numerous national and international TB treatment trials
  • Ajit Lalvani MA, DM, FRCP, Professor, Director, Tuberculosis Research Centre
  • National Heart and Lung Institute Imperial College London

Why is DAR-901 the most promising new TB vaccine?

  • SRL 172 is the only new TB vaccine to have progressed to Phase 3 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.

Recent studies with DAR-901

  • An animal challenge study published in late 2016 showed that a DAR-901 booster provided greater protection against TB than a BCG booster.
  • A human Phase 1 dose escalation trial demonstrated that a 3-injection series of DAR-901 was safe and well tolerated in humans and induced immune responses similar to those seen with the effective SRL172 vaccine.

Current 2b clinical trial with DAR-901

  • DAR-901 is currently being evaluated in the DAR-901-PIAT randomized, controlled Phase 2b study in Tanzania.
  • DAR-901-PIAT is a Prevention of Infection (POI) trial among 650 adolescents aged 13-15 in Dar es Salaam
  • All subjects completed 3 injections of vaccine or placebo by March 2017 confirming the safety and tolerability of immunization.
  • The trial will end in Q4 2018
  • DAR-PIA is supported by a grant from the Global Health innovative Technology Fund (GHIT, Japan)

What are the implications for global health?

An effective new TB vaccine would, literally, save millions of lives world-wide and is essential for achieving the goal of TB elimination by 2035

Contact information for pharmaceutical manufacturers and donors

Dartmouth offers options for interim support of DAR-901 or, for a qualified vaccine manufacturer, full acquisition of the license.
Full information and on-site presentations are available from Dr. Ford von Reyn ( This e-mail address is being protected from spambots. You need JavaScript enabled to view it )