Abstract
Visceral leishmaniasis is a major neglected lethal parasitic disease for which treatment options are scarce and toxicity, resistance and post-treatment relapse are common. No human vaccine is currently available and parasite quiescence is completely overlooked in the development of novel vaccination strategies. Our cutting-edge research has recently identified stem cells in the bone marrow as a sanctuary site where parasites can hide and survive drug treatment by transitioning to a quiescent state. Transcriptional profiling of quiescent and non-quiescent parasites provided differential genes, uniquely expressed during quiescence, that constitute attractive therapeutic vaccine antigen candidates. This project will provide unprecedented information about host-pathogen interactions and explore vaccination strategies to prevent relapse by: (i) obtaining essential data on antigenic presentation properties of Leishmania-infected stem cells, (ii) editing parasitic quiescence genes and selecting single domain antibodies (sdAbs) against quiescence gene products, and (iii) exploring immunity to quiescence genes during infection and following immunization. Taken together, it is expected that in-depth understanding of parasitic quiescence and corresponding antigenic/immunogenic properties will be revolutionary for the development of novel therapeutic vaccination strategies that can be incorporated with drug treatment to prevent relapse.
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