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TSA-1 C4 (also known as TSA-1.C4) is a recombinant protein subunit vaccine candidate under development for the treatment and prevention of Chagas disease, which is caused by the protozoan parasite *Trypanosoma cruzi*. The vaccine is based on the trypomastigote surface antigen 1 (TSA-1), a major surface antigen of *T. cruzi* that is a key target of protective humoral and cellular immune responses. To improve the stability, refolding, and scalability of the recombinant protein during manufacturing, the antigen was engineered with four cysteine-to-serine mutations (at positions 258, 277, 360, and 447), resulting in the 'C4' designation. TSA-1 C4 is typically formulated with a Toll-like receptor 4 (TLR-4) agonist adjuvant (such as E6020 or monophosphoryl lipid A) and has been evaluated both as a monotherapy and in combination with low-dose benznidazole (vaccine-linked chemotherapy) or alongside the Tc24-C4 antigen in a bivalent formulation. Preclinical studies in murine and canine models have demonstrated that TSA-1 C4 immunization induces robust antigen-specific CD4+ and CD8+ T-cell responses, reduces parasitemia, and prevents cardiac inflammation and fibrosis associated with chronic chagasic cardiomyopathy.
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