- RFP Year2018
- Awarded Amount$3,998,989
- DiseaseNTD (Leishmaniasis)
- Development StagePreclinical Development
- Collaboration PartnersInstitute of Tropical Medicine (NEKKEN) Nagasaki University , Gennova Biopharmaceuticals Ltd., McGill University , The Ohio State University
- Past Project
Zhang WW, Karmakar S, Gannavaram S, Dey R, Lypaczewski P, Ismail N, Siddiqui A, Simonyan V, Oliveira F, Coutinho-Abreu IV, DeSouza-Vieira T, Meneses C, Oristian J, Serafim TD, Musa A, Nakamura R, Saljoughian N, Volpedo G, Satoskar M, Satoskar S, Dagur PK, McCoy JP, Kamhawi S, Valenzuela JG, Hamano S, Satoskar AR, Matlashewski G, Nakhasi HL. A second generation leishmanization vaccine with a markerless attenuated Leishmania major strain using CRISPR gene editing. Nat Commun. 2020 Jul 10;11(1):3461. doi: 10.1038/s41467-020-17154-z. PMID: 32651371; PMCID: PMC7351751.
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, 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. Our team has developed a live attenuated vaccine for leishmaniasis by generating an attenuated dermotropic Leishmania by deleting a key gene to be critical for parasite virulence and persistence in the host.
The overall objective of this project is to advance the preclinical development of this vaccine candidate. The aims of this project are: 1) Undertake pre-clinical toxicology studies on the vaccine as per regulatory guidelines, 2) Manufacture clinical grade GMP vaccine for clinical trials.
Using CRISPR-Cas technology, we have successfully generated antibiotic selection marker free centrin gene deficient L. major (LmCen-/-) and have established their safety and efficacy in pre-clinical laboratory studies. Our team will produce LmCen-/- vaccine under GLP conditions, undertake pre-clinical toxicology testing in animals as per regulatory guidelines and manufacture sufficient quantities of clinical grade GMP LmCen-/- for clinical testing.
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, Gennova Biopharmaceuticals have developed a live attenuated vaccine against leishmaniasis. This project will further advance pre-clinical development of this vaccine candidate for human trials and will lead to a safe, affordable and effective vaccine against all forms of leishmaniasis. If successful, this vaccine can help reduce the global burden of leishmaniasis and achieve disease elimination.
What sort of innovation are you bringing in your project?
This is the first vaccine for leishmaniasis developed by generating a novel attenuated cutaneous disease causing species, centrin gene deficient L. major (LmCen-/-) using CRISPR-Cas technology. CRISPR-Cas enabled the development of attenuated strains as a defined product without antibiotic resistance genes and off target mutations that can advance to human trials.
Role and Responsibility of Each Partner
Gennova Biopharmaceuticals will produce LmCen-/- vaccine for clinical trials. The Ohio State University and Nagasaki University will evaluate the safety of LmCen-/- vaccine, and Nagasaki University will perform toxicology studies on LmCen-/- product manufactured by Gennova. McGill University will undertake genomic characterization of LmCen-/- vaccine. Scientists at US-FDA and NIAID/NIH will evaluate the efficacy of industry manufactured vaccine using select animal models of CL and VL. All partners will be involved in compiling documents for submission to regulatory authorities.