Grant: Operating Grant

Infectious diseases including those caused by parasites remain a leading cause of morbidity and mortality throughout the world, particularly in developing countries. With climate changes, increased traveling, immigration and military operations in endemic countries, Canadians are increasingly in contact with novel infections. Currently, about 350 million people the world are at risk of contracting Leishmaniasis, with 2 million new infections per year. Several species of th e parasite cause clinical disease manifestations ranging from self-healing cutaneous, disfiguring mucocutaneous, to fatal visceral leishmaniasis. In endemic areas, Leishmania is also found to be an opportunistic pathogen in HIV-1-infected patients. Indeed, it was estimated that AIDS increases the risk of visceral leishmaniasis by up to a 1,000-fold. There are no effective vaccines against leishmaniasis because we still do not fully understand the mechanisms of protective immunity, particularly those associated with secondary (memory) response. While recovery from natural or experimental infection results in development of long-lasting immunity to re-infection, vaccination with heat-killed L. major (as is currently practiced in some areas) induces only short-term protection. We have discovered that persistence of parasites at the site of primary infection is important for maintenance of immunity. We have engineered a non-pathogenic Leishmania that persists after infection, does not induce overt disease and protects mice against virulent challenge infections. The work proposed here will investigate the mechanisms of secondary anti-Leishmania immunity in mice. The results would define the factors that regulate the generation, maintenance and loss of secondary anti-Leishmania immunity. The findings may suggest new strategies for vaccine designs and vaccination against this other important diseases caused by intracellular pathogens including Malaria, Tuberculosis and HIV/AIDS.