{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T19:22:07Z","timestamp":1782760927292,"version":"3.54.5"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T00:00:00Z","timestamp":1700179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>During the COVID-19 pandemic we utilized an AI-driven T cell epitope prediction tool, the NEC Immune Profiler (NIP) to scrutinize and predict regions of T cell immunogenicity (hotspots) from the entire SARS-CoV-2 viral proteome. These immunogenic regions offer potential for the development of universally protective T cell vaccine candidates. Here, we validated and characterized T cell responses to a set of minimal epitopes from these AI-identified universal hotspots. Utilizing a flow cytometry-based T cell activation-induced marker (AIM) assay, we identified 59 validated screening hits, of which 56% (33 peptides) have not been previously reported. Notably, we found that most of these novel epitopes were derived from the non-spike regions of SARS-CoV-2 (Orf1ab, Orf3a, and E). In addition, <jats:italic>ex vivo<\/jats:italic> stimulation with NIP-predicted peptides from the spike protein elicited CD8<jats:sup>+<\/jats:sup> T cell response in PBMC isolated from most vaccinated donors. Our data confirm the predictive accuracy of AI platforms modelling <jats:italic>bona fide<\/jats:italic> immunogenicity and provide a novel framework for the evaluation of vaccine-induced T cell responses.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1265044","type":"journal-article","created":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T09:18:27Z","timestamp":1700299107000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Experimental validation of immunogenic SARS-CoV-2 T cell epitopes identified by artificial 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