Development & Manufacture of an MDR Tuberculosis Vaccine

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DESCRIPTION (provided by applicant): VACCINES FOR BIODEFENSE: We have identified several new TB vaccine candidate antigens based on human T cell responses and animal protection. Priority has been given to those that both elicit a Thl response from PBMC from PPD positive healthy donors and protect in rodent models. A non-human primate vaccine model has been established and is currently being used to further characterize vaccine candidates and adjuvant/delivery systems. We have developed Mtb72f in AS02A, the first defined TB vaccine to enter clinical trials. However, more recent data indicate that three other antigens may add to the protection obtained with Mtb 72f. Therefore, we have generated two additional polyproteins that incorporate these antigens on the Mtb72f backbone. The two new fusion proteins are Mtb92f and Mtbl 13f. Using validated rodent models of infection and disease we will select one of these antigens for GMP manufacture and clinical development. The selection process will emphasis both pre- and post-challenge immunization as criteria for prioritization. The selected candidate will be subjected to process development, including optimization of fermentation, development potency and stability assays of adjuvant (AS02A) formulated antigen. By the end of the funding period, we will have defined and developed a second generation vaccine candidate, collected data for MDR-TB, evaluated safety with a GLP toxicology study and manufactured vials under cGMPs. This will enable us to immediately proceed to human clinical trials after the end of the funding period.