Live attenuated leishmania parasite vaccines with enhanced safety characteristics
AssigneesThe U.S.A., as represented by the Secretary, Department of Health and Human Services, Ohio State Innovation Foundation
InventorsHira L. Nakhasi, Ranadhir Dey, Sreenivas Gannavaram, Subir Karmakar, Gregory Matlashewski, Abhay Satoskar, Wen-Wei Zhang, Patrick Lypaczewski
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Abstract
Disclosed herein are modified Leishmania species and compositions thereof, such as live, attenuated organisms, immunogenic compositions, vaccines, and pharmaceutical compositions. Further disclosed are methods related to the modified Leishmania species, such as methods of production and methods of use.
Claims6
A live, attenuated cutaneous or mucocutaneous Leishmania species comprising at least one genetic modification, wherein the at least one genetic modification comprises an amastigote growth-arresting modification comprising a functional deletion or genetic inactivation of the centrin, kharon1, biopterin transporter 1 (Bt1), p27, Lipophosphoglycan biosynthetic protein 2 (Lpg-2), ubiquitin fold modifier-1 (Ufm-1), or Ufm1 processing peptidase (Ufsp) gene.
A method of producing an immunogenic composition, comprising:
- introducing a first nucleic acid encoding a selection marker and gene-editing complex into Leishmania promastigotes;
- selecting Leishmania promastigotes with the selection marker;
- culturing the Leishmania promastigotes with the selection marker;
- and
- selecting Leishmania promastigotes with a slow-growing phenotype.
Dependencies are inferred from the claim text.