{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T03:59:08Z","timestamp":1782964748008,"version":"3.54.5"},"reference-count":91,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Southern Star Medical Research Institute"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Trypanosoma cruzi<\/jats:italic> is a protozoan parasite that causes Chagas disease. Globally 6 to 7 million people are infected by this parasite of which 20\u201330% will progress to develop Chronic Chagasic Cardiomyopathy (CCC). Despite its high disease burden, no clinically approved vaccine exists for the prevention or treatment of CCC. Developing vaccines that can stimulate <jats:italic>T<\/jats:italic>. <jats:italic>cruzi<\/jats:italic>-specific CD8+ cytotoxic T cells and eliminate infected cells requires targeting parasitic antigens presented on major histocompatibility complex-I (MHC-I) molecules. We utilized mass spectrometry-based immunopeptidomics to investigate which parasitic peptides are displayed on MHC-I of <jats:italic>T<\/jats:italic>. <jats:italic>cruzi<\/jats:italic> infected cells. Through duplicate experiments, we identified an array of unique peptides that could be traced back to 17 distinct <jats:italic>T<\/jats:italic>. <jats:italic>cruzi<\/jats:italic> proteins. Notably, six peptides were derived from Tcj2, a trypanosome chaperone protein and member of the DnaJ (heat shock protein 40) family, showcasing its potential as a viable candidate vaccine antigen with cytotoxic T cell inducing capacity. Upon testing Tcj2 as an mRNA vaccine candidate in mice, we observed a strong memory cytotoxic CD8+ T cell response along with a Th1-skewed humoral antibody response. <jats:italic>In vitro<\/jats:italic> co-cultures of <jats:italic>T<\/jats:italic>. <jats:italic>cruzi<\/jats:italic> infected cells with splenocytes of Tcj2-immunized mice restricted the replication of <jats:italic>T<\/jats:italic>. <jats:italic>cruzi<\/jats:italic>, demonstrating the protective potential of Tcj2 as a vaccine target. Moreover, antisera from Tcj2-vaccinated mice displayed no cross-reactivity with DnaJ in lysates from mouse and human indicating a decreased likelihood of triggering autoimmune reactions. Our findings highlight how immunopeptidomics can identify new vaccine targets for Chagas disease, with Tcj2 emerging as a promising new mRNA vaccine candidate.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012764","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T18:32:38Z","timestamp":1734546758000},"page":"e1012764","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Immunopeptidomic MHC-I profiling and immunogenicity testing identifies Tcj2 as a new Chagas disease mRNA vaccine candidate"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5250-5746","authenticated-orcid":true,"given":"Leroy","family":"Versteeg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh","family":"Adhikari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonteria","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jungsoon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfei","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelufa","family":"Islam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Keegan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William K.","family":"Russell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Poveda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jose","family":"Villar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Elena","family":"Bottazzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hotez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"Tijhaar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1420-4015","authenticated-orcid":true,"given":"Jeroen","family":"Pollet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,12,18]]},"reference":[{"key":"ppat.1012764.ref001","article-title":"Chagas Disease: From Discovery to a Worldwide Health Problem","volume":"7","author":"KCF Lidani","year":"2019","journal-title":"Front Public Health"},{"issue":"1","key":"ppat.1012764.ref002","doi-asserted-by":"crossref","first-page":"59","DOI":"10.5334\/gh.1150","article-title":"Global, Regional, and National Trends of Chagas Disease from 1990 to 2019: Comprehensive Analysis of the Global Burden of Disease Study","volume":"17","author":"SA G\u00f3mez-Ochoa","year":"2022","journal-title":"Glob Heart"},{"issue":"0","key":"ppat.1012764.ref003","first-page":"1","article-title":"Preclinical advances and the immunophysiology of a new therapeutic Chagas disease vaccine","volume":"0","author":"KM Jones","year":"2022","journal-title":"Expert Rev Vaccines"},{"issue":"10115","key":"ppat.1012764.ref004","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/S0140-6736(17)31612-4","article-title":"Chagas disease","volume":"391","author":"JA P\u00e9rez-Molina","year":"2018","journal-title":"The Lancet"},{"key":"ppat.1012764.ref005","unstructured":"Neglected Infectious Diseases in the Americas: Success Stories and Innovation to Reach the Neediest\u2014PAHO\/WHO | Pan American Health Organization [Internet]. 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