NPJ vaccinesFeb 19, 2026

Next-generation SARS-CoV-2 vaccine mRNA-1283 produces strong and long-lasting T cell immune responses with lower doses

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 28, 2026

Abstract

Essence

In healthy COVID-19-naive adults, two low-dose mRNA-1283 shots produced durable polyfunctional SARS-CoV-2 T cell responses comparable to standard-dose mRNA-1273 through Day 209.

Evidence

This phase 1 randomized clinical trial in adults aged 18-55 compared mRNA-1283 regimens with 100 ug mRNA-1273 using intracellular cytokine staining and TCRbeta sequencing, showing sustained Th1-biased CD4+ and CD8+ responses.

Caveat

The study was a small phase 1 immunogenicity trial in healthy adults and measured cellular immune markers rather than clinical protection against COVID-19.

Simplified

Cell-mediated immunity contributes to durable protection against severe COVID-19, particularly as antibody responses wane or viral variants partially evade neutralization. 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-naïve, healthy adults (18-55 years) received two doses of mRNA-1283 (10 µg, 30 µg, or 100 µg), two doses of mRNA-1273 (100 µg; 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+ T cell responses that were maintained through Day 209. TCRβ 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 µg) regimen of the next-generation COVID-19 vaccine, mRNA-1283, induces polyfunctional and durable CD4+ and CD8+ T cell immunity comparable to the standard 100 µg mRNA-1273 vaccine, supporting a dose-sparing strategy without compromising long-term cellular protection against severe COVID-19.

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Next-generation SARS-CoV-2 vaccine mRNA-1283 produces strong and long-lasting T cell immune responses with lower doses

Abstract

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