The time has come for a vaccine against Chagas disease

Abstract

Despite many studies, there is still no vaccines for Chagas Disease (CD), which affects approximately 7 million people mainly in Latin America. To make matters worse, the only two drugs available have proved efficacy only when administered during the acute phase of the disease. Here, we discuss recent advances towards the development of a CD vaccine including (i) better understanding of the role of elements involved in immune responses and host defense against Trypanosoma cruzi; (ii) molecular characterization of parasite genetic diversity and the biochemical nature of T. cruzi antigens involved in protective immune responses; and (iii) the use of novel vaccine platforms that show high efficacy in experimental models. Other aspects such as the role of parasite-induced inflammation in the pathogenesis of CD is also under intense scrutiny. An essential issue discussed in this Viewpoint refers to the main use of a vaccine for CD, i.e., whether this vaccine should be used for prophylactic purposes, combined therapy to improve drug efficacy and parasitological cure, or to re-orient the immune and inflammatory response. Finally, we emphasize the necessity to attract the interest of both private and public pharmaceutical companies to translate all the pre-clinical studies into a much-needed CD vaccine.

Keywords: Chagas disease; Immune response; Prophylactic vaccine; Therapeutic vaccine.

Fig. 1

Expected outcomes and challenges in different protocols for a CD vaccine. The curve represents the course of the infection, with an acute phase and a chronic phase. The main vaccine protocols for CD, one for a prophylactic vaccine and two therapeutic vaccine protocols are represented. A prophylactic vaccine, represented on the left part of the figure (green section), is intended for administration prior to infection. The two proposed therapeutic vaccines protocols indicated on the right (yellow sections), are designed for patients with chronic infection. One protocol is aimed at asymptomatic patients, while the other targets individuals exhibiting symptoms of chronic disease. Arrows indicate potential outcomes of immunization, while the question marks underscore the challenges associated with each vaccination protocol. Created in BioRender. Castro, J. (2025) https://BioRender.com/y26u221.