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- Title
Immunization with a Trypanosoma cruzi cyclophilin-19 deletion mutant protects against acute Chagas disease in mice.
- Authors
Jha, Bijay Kumar; Varikuti, Sanjay; Verma, Chaitenya; Shivahare, Rahul; Bishop, Nicholas; Dos Santos, Gregory P.; McDonald, Jacquelyn; Sur, Aakash; Myler, Peter J.; Schenkman, Sergio; Satoskar, Abhay R.; McGwire, Bradford S.
- Abstract
Human infection with the protozoan parasite Trypanosoma cruzi causes Chagas disease for which there are no prophylactic vaccines. Cyclophilin 19 is a secreted cis-trans peptidyl isomerase expressed in all life stages of Trypanosoma cruzi. This protein in the insect stage leads to the inactivation of insect anti-parasitic peptides and parasite transformation whereas in the intracellular amastigotes it participates in generating ROS promoting the growth of parasites. We have generated a parasite mutant with depleted expression of Cyp19 by removal of 2 of 3 genes encoding this protein using double allelic homologous recombination. The mutant parasite line failed to replicate when inoculated into host cells in vitro or in mice indicating that Cyp19 is critical for infectivity. The mutant parasite line also fails to replicate in or cause clinical disease in immuno-deficient mice further validating their lack of virulence. Repeated inoculation of mutant parasites into immuno-competent mice elicits parasite-specific trypanolytic antibodies and a Th-1 biased immune response and challenge of mutant immunized mice with virulent wild-type parasites is 100% effective at preventing death from acute disease. These results suggest that parasite Cyp19 may be candidate for small molecule drug targeting and that the mutant parasite line may warrant further immunization studies for prevention of Chagas disease.
- Subjects
CHAGAS' disease; TRYPANOSOMA cruzi; ACUTE diseases; IMMUNIZATION; PROTOZOAN diseases; ISOMERASES
- Publication
NPJ Vaccines, 2023, Vol 8, Issue 1, p1
- ISSN
2059-0105
- Publication type
Article
- DOI
10.1038/s41541-023-00647-5