Live attenuated Leishmania parasite vaccines with enhanced safety characteristics
AssigneesThe United States of America, 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.
Claims16
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 gene, and wherein the Leishmania species does not comprise any off-target genomic deletions, wherein the Leishmania species comprises:
- (i) at least one guide RNA (gRNA) comprising SEQ ID NO:
- 11 or SEQ ID NO:
- 12;
- (ii) a pLdCN vector encoding a Cas9 enzyme;
- or
- (iii) both (i) and (ii).
A live, attenuated cutaneous or mucocutaneous Leishmania species comprising a functional deletion or genetic inactivation of the centrin gene, wherein the Leishmania species does not comprise an antibiotic-resistance gene, and wherein the Leishmania species comprises:
- (i) at least one guide RNA (gRNA) comprising SEQ ID NO:
- 11 or SEQ ID NO:
- 12;
- (ii) a pLdCN vector encoding a Cas9 enzyme;
- or
- (iii) both (i) and (ii).
Dependencies are inferred from the claim text.