Discussion

Chagas disease, caused by Trypanosoma cruzi, affects 6-8 million people. Those who develop chronic stage pathology often suffer severe, life-threatening cardiac and/or gastrointestinal symptoms. The current drugs can have severe side effects and treatment failures are frequently reported. Pre-clinical testing of vaccine candidates has been limited by the complex nature of the disease and difficulties in detecting the extremely low parasite burden during chronic infections. Here, we describe a new murine model for vaccine testing, based on highly sensitive bioluminescence imaging, which circumvents these problems and provides new insights into conferred immunity. In preliminary experiments, mice were infected with bioluminescent T. cruzi, cured by benznidazole treatment, and then subjected to re-infection. The mice were found to be highly resistant to re-infection with the same strain, whereas cross-strain immunity, although effective at reducing the parasite burden, was insufficient to confer sterile protection. We next assessed if the level of protection was influenced by the route of inoculation or the length of the primary infections. The data demonstrate that this predictive model can be used to establish the correlates of protection, and that it can have a central role in studying the efficacy of recombinant vaccines, and the relative merits of prophylactic and therapeutic vaccines as strategies for combatting this complex parasitic infection.