Use of Leishmania major parasites expressing a recombinant Trypanosoma cruzi antigen as live vaccines against Chagas disease

is the protozoan parasite causing Chagas disease, a Neglected Tropical Disease that affects 8 million people and causes 12,000 deaths per year, primarily because of cardiac pathology. Effective vaccination for remains an elusive goal. The use of a live vaccine vector, especially one that mimics the pathogen target, may be superior to the use of recombinant protein or DNA vaccine formulations. We generated recombinant , a related trypanosomatid parasite, as a vaccine vehicle to express the immunogenic -sialidase (TS) antigen. The induction of T cell and antibody responses, as well as protective immunity generated by these vaccines were assessed in vivo. We demonstrate that mice inoculated with these recombinant TS-expressing parasites mount T cell and antibody responses directed against TS and are protected against future infection. We also show that the partially attenuated . major strain, previously found to induce protective immunity to virulent infection without causing pathology, can also be engineered to express the TS antigen. This latter recombinant may represent a safe and effective option to explore for ultimate use in humans. Altogether, these data indicate that can stably express a antigen and induce -specific protective immunity, warranting further investigation of attenuated Leishmania parasites as vaccine.