Live attenuated prophylactic vaccine for leishmaniasis
  • Awarded Year
    2015
  • Awarded Amount
    $1,832,967
  • Disease
    NTDs Leishmaniasis
  • Intervention
    Vaccine
  • Development Stage
    Lead Optimization
  • Collaboration Partners
    Institute of Tropical Medicine (NEKKEN) Nagasaki University , McGill University , The Ohio State University

Introduction and Background of the Project

The leishmaniases comprise a number of diseases caused by obligate intracellular parasites of the genus Leishmania that is transmitted by the bites of infected sandflies. With over 350 million people worldwide at risk of contracting leishmaniasis and, the WHO classifies leishmaniasis as a neglected tropical disease. Visceral leishmaniasis (VL) is the most severe form of the disease which is fatal without treatment. It is well documented that patients who recover from leishmaniasis including VL develop protective immunity against reinfection, which altogether indicates that a vaccine is feasible. The goal of this project is to: 1) develop a live attenuated prophylactic vaccine against leishmaniasis by generating attenuated dermotropic Leishmania by deleting a key gene that was identified by our team member US-FDA to be critical for parasite virulence and persistence in the host and 2) test the safety and efficacy of the live attenuated vaccine using a mouse model of VL as well as sand fly transmitted infection model in hamsters which mimics natural infection.

How can your partnership (project) address global health challenges?

No licensed human vaccine is currently available for leishmaniasis. The Ohio State University with its partners Nagasaki University, McGill University, US FDA and NIAID/NIH is undertaking effort to develop a safe, affordable and effective vaccine against all forms of leishmaniasis. If successful, this vaccine can help reduce the global burden of leishmaniasis.  

What sort of innovation are you bringing in your project?

The Ohio State University and Nagasaki University have developed innovative technologies for analyzing immune responses in animal models. McGill University has successfully established CRISPR-Cas9 technology for generating attenuated Leishmania by genome editing. US-FDA and NIAID/NIH are the premiere institutions who have developed, and identified biomarkers of immunity of genetically modified live attenuated Leishmania parasites as well as a vector transmitted infection in hamsters for testing the vaccine candidate.

Role and Responsibility of Each Partner

Nagasaki University's Institute for Tropical Medicine will be responsible for optimizing vaccine dose and regimen and characterizing the immune responses induced by the vaccine using a preclinical mouse model of VL caused by virulent L. donovani. The Ohio State University with their collaboration partners US-FDA and NIH will be responsible for analysis and characterization of attenuated centrin deficient Leishmania in vitro, evaluation of the efficacy of these parasites as a vaccine against visceral leishmaniasis (VL) using an experimental model of sand fly-transmitted VL in hamsters, determination of adjuvant requirement, analysis of magnitude and duration of memory T cell response after vaccination and overall project management and reporting. The McGill University will generate centrin gene deficient L. major and L. mexicana using CRISPR-Cas9 technology. 

 

The Ohio State University with their collaboration partners US-FDA and NIH will be responsible for analysis and characterization of attenuated centrin deficient Leishmania in vitro, evaluation of the efficacy of these parasites as a vaccine against visceral leishmaniasis (VL) using an experimental model of sand fly-transmitted VL in hamsters, determination of adjuvant requirement, analysis of magnitude and duration of memory T cell response after vaccination and overall project management and reporting. The McGill University will generate centrin gene deficient L. major and L. mexicana using CRISPR-Cas9 technology. Nagasaki University Institute for Tropical Medicine will be responsible for optimizing vaccine dose and regimen and characterizing the immune responses induced by the vaccine using a preclinical mouse model of VL caused by virulent L. donovani.