Grant: Project Grant

Tuberculosis (TB), is a mycobacterial infection that is one of the world's most pressing health problems. Each day, 5,000 people die from TB globally. The World Health Organization (WHO) reports that TB will infect 225 million and kill 75 million people between 2015-2050. TB spreads by aerosol through sneezing and coughing, and each person with TB infects ~15 more people/yr. The lack of an effective vaccine, the lengthy treatments with multiple drugs that have serious side effects, the prevalence of co-infection with HIV and the increasing number of cases of multi- and extensively- drug-resistant TB (MDR/XDR-TB), have made the control of TB highly challenging whether in developed or developing countries worldwide. Traditional antibiotics directly target and kill the mycobacteria after infection, but these have proven insufficient to curb this disease and have resulted in the emergence of incurable, totally drug resistant TB, (TDR-TB), putting this disease on high alert by WHO. There is a clear association between the immune status of an individual, the outcome of infection and reactivation of TB disease. It is crucial to find efficient host-based therapies if we are to conquer dreaded MDR, XDR and TDR-TB. Recently, we have discovered a novel immunotherapeutic that significantly reduces mycobacterial loads in mice. In the proposed work we will investigate its antimycobacterial potential in conjunction with modified Mtb antigens to enhance Mtb-specific host immunity, and in combination with the current anti-TB drugs. These studies will contribute significantly to the investigation of new approaches, and identification of new therapeutic regimens to treat active TB, MDR-, XDR- and TDR-TB infections, and will have major impact on the health of Canadians and people worldwide.