Optimization and pre-clinical development of a Trypanosoma cruzi CYP19 knock-out strain as a live vaccine for Chagas disease

This project will lead to the development of a vaccine against Chagas disease, which affects millions of people living in endemic areas in Central and South America. The long-term goal of this work is to generate a safe and highly efficacious live attenuated vaccine for Chagas disease for use in humans and in animals. The specific objectives are: 1) engineering a Cyp19 DKO (CC-DKO) vaccine strain using CRISPR/Cas9 and confirming its potential to provide protection in mice; 2) understanding of the T- and B-cell response responsible for protective immunity generated by this vaccine strain; 3) demonstrating that the CC-DKO vaccine is efficacious at preventing acute and chronic Chagas disease in mice and cross-protects from multiple strains and understand the duration of immunity; 4) understanding if the vaccine is safe in immunosuppressed hosts; and 5) understand if the CC-DKO is transmissible through the insect vector.