Induction of Sustained Immunity Following Vaccination with Live Attenuated Trypanosoma cruzi Parasites Combined with Saponin-Based Adjuvants

Chagas disease, caused by <i>Trypanosoma cruzi</i>, remains a major health concern in Latin America, particularly affecting low-income and rural communities. Among the many vaccine strategies explored, live attenuated parasites have shown the strongest ability to trigger protective immune responses. In this study, we investigated whether adding saponin-based adjuvants-Immunostimulant Particle Adjuvant (ISPA) and Quil-A-could improve the effectiveness and safety of a live parasite attenuated <i>T. cruzi</i> vaccine. Mice were vaccinated with a <i>T. cruzi</i> attenuated strain (TCC) alone or in combination with each adjuvant, and immunoglobulin G (IgG) subtypes in the serum of vaccinated mice, and interferon gamma (IFN-γ) and interleukin-10 (IL-10) in the supernatants of stimulated cells were measured at two weeks and twelve months post-vaccination. While protection levels were similar across all groups, the adjuvants assist in modulating the immune response over time: ISPA and Quil-A initially shifted antibody production toward IgG1 but later favored a balanced T_H1/T_H2 profile. ISPA also promoted long-term regulation through increased IL-10. Both adjuvants reduced tissue inflammation and enhanced clearance of vaccine-derived parasites. These findings suggest that while adjuvants may not boost protection directly, they significantly improve vaccine safety and immune quality, reinforcing their value in developing better vaccines for Chagas disease.