Epitope mapping of vaccine antigens Tc24 and TSA1 with antibodies from Trypanosoma cruzi-infected patients

Chagas disease is a zoonotic disease caused by Trypanosoma cruzi parasites. Tc24 and TSA1 parasite antigens are leading candidates for a therapeutic vaccine to treat infected patients to stop/delay the progression of chronic cardiomyopathy. As these antigens are nearing clinical trials, we aimed to assess their epitope recognition profile by antibodies from Chagas disease patients to better understand their immunogenicity in humans. Peptide microarrays covering Tc24-C4 and TSA1-C4 vaccine antigens were incubated with IgG from 27 T. cruzi-infected patients from Argentina, Honduras and Mexico. Most patients (20/27, 74%) had a highly similar recognition profile of both vaccine antigens, with the same immunodominant epitopes (three epitopes for Tc24-C4 and four for TSA1-C4). Remaining patients had limited reactivity against these antigens, targeting epitopes that varied among patients. All immunodominant epitopes were well conserved among T. cruzi strains and DTUs, and most were accessible on the surface of the proteins. The immunodominant epitope recognition profile was observed independently of patient HLA profile, diagnostic test reactivity or T. cruzi parasite burden. Patients were infected with mixtures of TcI, TcII, TcIV, TcV and TcVI parasites. These results present an important baseline for assessing potential changes in epitope profiles following therapeutic vaccination in future clinical trials.