Reaching for the Holy Grail: insights from infection/cure models on the prospects for vaccines for Trypanosoma cruzi infection

Prevention of Trypanosoma cruzi infection in mammals likely dependson either prevention of the invading trypomastigotes from infecting host cells or therapid recognition and killing of the newly infected cells by T.cruzi-specific T cells. We show here that multiple rounds of infectionand cure (by drug therapy) fails to protect mice from reinfection, despite thegeneration of potent T cell responses. This disappointing result is similar to thatobtained with many other vaccine protocols used in attempts to protect animalsfrom T. cruzi infection. We have previously shown that immunerecognition of T. cruzi infection is significantly delayed both atthe systemic level and at the level of the infected host cell. The systemic delayappears to be the result of a stealth infection process that fails to triggersubstantial innate recognition mechanisms while the delay at the cellular level isrelated to the immunodominance of highly variable gene family proteins, in particularthose of the trans-sialidase family. Here we discuss how these previous studies andthe new findings herein impact our thoughts on the potential of prophylacticvaccination to serve a productive role in the prevention of T. cruziinfection and Chagas disease.