Leishmaniasis is a neglected tropical disease caused by Leishmania protozoa transmitted by infected sand flies. Vaccination through leishmanization with live Leishmania major has been used successfully but is no longer practiced because it resulted in occasional skin lesions. A second generation leishmanization is described here using a CRISPR genome edited L. major strain (LmCen). Notably, LmCen is a genetically engineered centrin gene knock-out mutant strain that is antibiotic resistant marker free and does not have detectable off-target mutations. Mice immunized with LmCen have no visible lesions following challenge with L. major-infected sand flies, while non-immunized animals develop large and progressive lesions with a 2-log fold higher parasite burden. LmCen immunization results in protection and an immune response comparable to leishmanization. LmCen is safe since it is unable to cause disease in immunocompromised mice, induces robust host protection against vector sand fly challenge and because it is marker free, can be advanced to human vaccine trials.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351751PMC
http://dx.doi.org/10.1038/s41467-020-17154-zDOI Listing

Publication Analysis

Top Keywords

second generation
8
generation leishmanization
8
leishmania major
8
major strain
8
sand flies
8
marker free
8
lmcen
5
leishmanization
4
leishmanization vaccine
4
vaccine markerless
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!