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Here, we characterize SARS-CoV-2-specific T cell responses elicited by a next-generation COVID-19 vaccine, mRNA-1283, which encodes the receptor-binding and N-terminal domains of the spike protein, in a phase 1 randomized clinical trial (NCT04813796). COVID-19-na\u00efve, healthy adults (18\u201355 years) received two doses of mRNA-1283 (10\u2009\u00b5g, 30\u2009\u00b5g, or 100\u2009\u00b5g), two doses of mRNA-1273 (100\u2009\u00b5g; full-length spike comparator), or a single-dose regimen of mRNA-1283. Using intracellular cytokine staining, we show that two-dose regimens of mRNA-1283 or mRNA-1273 induce Th1-biased, polyfunctional spike-specific CD4+ and CD8+\u2009T cell responses that were maintained through Day 209. TCR\u03b2 sequencing demonstrated significant increases in the breadth and frequency of SARS-CoV-2-associated TCRs, which correlated with functional spike-specific T cell responses. Therefore, the low-dose (10\u2009\u00b5g) regimen of the next-generation COVID-19 vaccine, mRNA-1283, induces polyfunctional and durable CD4+ and CD8+\u2009T cell immunity comparable to the standard 100\u2009\u00b5g mRNA-1273 vaccine, supporting a dose-sparing strategy without compromising long-term cellular protection against severe COVID-19.<\/jats:p>","DOI":"10.1038\/s41541-026-01402-2","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T14:30:09Z","timestamp":1771511409000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Potent and dose-sparing next-generation SARS-CoV-2 vaccine, mRNA-1283, induces polyfunctional and durable T cell immunity"],"prefix":"10.1038","volume":"11","author":[{"given":"Yamuna D.","family":"Paila","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolando","family":"Pajon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Banbury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Fields","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha","family":"Maglinao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C.","family":"De Rosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daryl","family":"Morris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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