Preparing for tuberculosis vaccine efficacy trials: Baseline epidemiology, improved diagnosis, markers of protection and phase I/II trials

This collaboration between scientists in Denmark, India, Norway, South Africa and the U. S. will conduct 3 large cohort studies of tuberculosis (TB) in Palamaner, India, using state of the art immunology to identify correlates of protective immunity and i ncipient disease. These cohorts will be augmented by a fourth study on improving vaccine delivery at the level of local clinics. The data and experience gained in these studies will be used for phase I and II trials of a new recombinant BCG vaccine, desig ned as part of a prime-boost regimen to prevent TB in children and in adults. The project will involve Norwegian support for the above-mentioned studies and for transfer of expertise to Serum Institute of India for new TB vaccine manufacturing processes , Indian Phase I and II trials of the vaccine, preparing for a phase III (efficacy) trial to be initiated at the end of this program, evaluating the use of commercially-available interferon-gamma release assays (IGRA) to identify persons with TB infection or TB disease in an endemic setting, identification of surrogate markers of vaccine-induced protection and genetic characterization of Mycobacterium tuberculosis strains in the study area to permit proper interpretation of phase III data as well as suppo rt for field site development and training. Arrangements are in place for worldwide distribution of this new vaccine regimen with access for the developing world at affordable prices. By tying immunology, field studies and vaccine development into a coh esive plan, we will develop a research program that is not dependant on long-term studies to start paying dividends, and that could attract funding to be self-sustaining beyond the proposed research project.