Vaccines against chronic Trypanosoma cruzi infection: progress, challenges and future directions

Chronic infections with Trypanosoma cruzi can lead to Chagas disease, with cardiac and/or digestive debilitating manifestations. There has been a renewed interest in vaccine development against this neglected tropical disease in the past decades.

Vaccines ranging from live attenuated to recombinant subunit, nucleic acid, bacterial, viral and algal vectors, targeting various parasite antigens have been tested in mice as preventative and therapeutic vaccine against clinical disease progression as well as in the context of pregnancy to prevent congenital transmission and other adverse birth outcomes. A few of these vaccine candidates have been tested in dogs and non-human primates. Further clinical development faces several challenges associated with slow disease progression and the lack of biomarkers, the diversity of parasite strains, complex host-parasite relationship, among others.

Pre-clinical studies broadly support the clinical development of a Chagas disease vaccine, particularly for a therapeutic vaccine. Synergy with drug development efforts, which face many of the same challenges, may provide new opportunities to strengthen clinical development and trials of drugs, vaccines and combined therapies.