Tuberculosis (TB) still remains a major global health threat; worldwide, it is responsible for over 3 million deaths annually. In lieu of the emerging multi-drug resistant Mycobacterium tuberculosis strains, control of TB through an effective vaccination is of a paramount importance. Although Mycobacterium bovis strain BCG is widely used for TB prophylaxis, its protective effect has recently been shown to be far below the necessary level to protect populations efficiently. A strong ThI type of cell mediated immune response is crucial for protection against M. tuberculosis infections. Several proteins of M. tuberculosis that are involved in stimulating a protective immune response have been identified and their genes have been cloned and sequenced. The overall objective of the proposed research project is to develop a highly efficacious and safe vaccine for TB. Specifically, the company proposes to prepare an effective vaccine against tuberculosis by expressing previously identified protective protein(s) of M. tuberculosis in Brucella abortus strain RB51, a bacterial vector with unique adjuvant properties and can stimulate a strong Th1 type of immune response. In the phase I part of the project, the company intends to i) construct recombinant RB51 strains that express 85A and ESAT-6 antigens of M. tuberculosis and ii) immunize mice with irradiated recombinant RB51 vaccines and characterize their antigen-specific antibody and cell-mediated immune responses to confirm that a Th1 type of immune response is induced.
