Grant: Project Grant

Human leishmaniasis are a complex spectrum of diseases affecting over 12 million people with an estimated 350 million people at risk of becoming infected globally. The effects of the disease range from small self-healing skin ulcers and lesions to large disfiguring scars or even death, depending on the species of Leishmania involved. Despite this significant health and societal burden, there is currently no effective vaccine against the disease. Worse still, the existing treatments either cause major side effects or are only effective in specific circumstances. The lack of effective vaccine is mostly attributed to the poor understanding of factors that regulate the development, maintenance and loss of secondary immunity. Interestingly, humans and animals that recover from infection remain immune for life, suggesting that memory cells able to protect against secondary infection develop following recovery from primary infection. Using reverse immunology and proteomics techniques, we identified a highly conserved protein that provides striking protection in vaccinated mice. With the help of collaborators around the globe, we demonstrated this protein also induces strong immune response in human patients. These studies subsequently led to the development of first Leishmania-specific reagent called tetramers, which is capable of identifying Leishmania-specific T cells at single cell level over an entire course of infection. It also helped to show that majority of the immune response is directed towards this protein. This unique reagent helped us to generate transgenic mice whose T cells all express receptor for this particular protein. We are now poised to use these animals to address fundamental questions regarding the factors that regulate antigen-specific memory response in leishmaniasis. Understanding these factors is critical to developing effective vaccine and vaccination strategies against leishmaniasis.