Characterization of a new Leishmania major isolate for use in a controlled human infection model

Ashwin, H.; Sadlova, J.; Vojtkova, B.; Becvar, T.; Lypaczewski, P.; Schwartz, E.; Greensted, E.; Van Bocxlaer, K.; Pasin, M.; Lipinski, K.; Parkash, V.; Matlashewski, G.; Layton, A.; Lacey, C.; Jaffe, C.; Volf, P.; Kaye, P.

doi:10.1101/2020.08.12.245936

bioRxiv · 10.1101/2020.08.12.245936

Characterization of a new Leishmania major isolate for use in a controlled human infection model

Ashwin, H.·Sadlova, J.·Vojtkova, B.·Becvar, T.·Lypaczewski, P.·Schwartz, E.·Greensted, E.·Van Bocxlaer, K.·Pasin, M.·Lipinski, K.·Parkash, V.·Matlashewski, G.·Layton, A.·Lacey, C.·Jaffe, C.·Volf, P.·Kaye, P.

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Abstract

Leishmaniasis is widely regarded as a vaccine-preventable disease, but the costs required to reach pivotal Phase 3 studies and uncertainty about which candidate vaccines should be progressed into human studies significantly limits progress in vaccine development for this neglected tropical disease. Controlled human infection models (CHIM) provide a pathway for accelerating vaccine development and to more fully understand disease pathogenesis and correlates of protection. Here, we describe the isolation, characterization and GMP manufacture of a new clinical isolate of Leishmania major. Two fresh isolates of L. major from Israel were initially compared by genome sequencing, in vivo infectivity and drug sensitivity in mice, and development and transmission competence in sand flies, allowing one (L. major_MRC-02) to be selected for GMP production. This study addresses a major roadblock in the development of vaccines for leishmaniasis, providing a key resource for CHIM studies of sand fly transmitted cutaneous leishmaniasis.

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Ashwin, H., Sadlova, J., Vojtkova, B., Becvar, T., Lypaczewski, P., Schwartz, E., Greensted, E., Van Bocxlaer, K., Pasin, M., Lipinski, K., Parkash, V., Matlashewski, G., Layton, A., Lacey, C., Jaffe, C., Volf, P., Kaye, P.. 2020-08-12. Characterization of a new Leishmania major isolate for use in a controlled human infection model. https://doi.org/10.1101/2020.08.12.245936

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