A Trypanosoma cruzi trans-sialidase peptide demonstrates high serological prevalence among infected populations across endemic regions

BACKGROUNDInfection by Trypanosoma cruzi, the agent of Chagas disease, is endemic to the Americas and can irreparably damage the cardiac and gastrointestinal systems during decades of parasite persistence. Diagnosis of chronic infection requires confirmation by multiple serological assays due to the imperfect performance of existing tests. Current serology tests were developed using small specimen sets predominantly from South America, and lower performance has been observed in patients who acquired infection in Central America and Mexico.METHODSTo improve Chagas disease serology, we evaluated antibody responses against the entire T. cruzi proteome with phage display immunoprecipitation sequencing and further evaluated high-prevalence antigens by immunoassay. We utilized specimen sets representing Mexico, Central America, and South America and varying cardiac disease presentations, from 185 cases and 143 controls.RESULTSWe identified over 1,300 antigenic T. cruzi peptides. A trans-sialidase antigen demonstrated high seroprevalence across all regions and has not previously been described as a diagnostic target to our knowledge. Orthogonal validation of this peptide demonstrated increased antibody reactivity for infections originating from Central America.CONCLUSIONThis study provides proteome-wide identification of seroreactive T. cruzi peptides across a range of endemic populations not previously represented in antigen discovery and identifies a trans-sialidase peptide antigen (TS23) with potential for translation into diagnostic serological assays.FUNDINGChan Zuckerberg Biohub, the Chan Zuckerberg Biohub Physician-Scientist Fellowship Program, the NIH National Heart Lung and Blood Institute award K38HL154203, and the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development award F30HD117526.