Next-Generation COVID-19 Vaccine mRNA-1283 Shows Dose-Sparing Potential in Phase 1 Trial
A phase 1 clinical trial demonstrates that mRNA-1283, a next-generation COVID-19 vaccine encoding receptor-binding and N-terminal domains of the spike protein, induces durable T cell immunity at a 10 µg dose comparable to the standard 100 µg mRNA-1273 vaccine.
A next-generation COVID-19 vaccine, mRNA-1283, induces polyfunctional and durable T cell immunity at significantly lower doses than the current standard vaccine, according to results from a phase 1 randomized clinical trial (NCT04813796). The vaccine encodes the receptor-binding and N-terminal domains of the spike protein, rather than the full-length spike protein used in mRNA-1273.
COVID-19-naïve, healthy adults aged 18–55 years received two doses of mRNA-1283 at 10 µg, 30 µg, or 100 µg, two doses of mRNA-1273 at 100 µg as a full-length spike comparator, or a single-dose regimen of mRNA-1283. Using intracellular cytokine staining, researchers showed 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. The low-dose 10 µg regimen of 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.
Cell-mediated immunity contributes to durable protection against severe COVID-19, particularly as antibody responses wane or viral variants partially evade neutralization. Access to patient-level data presented in the study and supporting clinical documents with external researchers who provide methodologically sound scientific proposals will be available upon reasonable request for products or indications that have been approved by regulators in the relevant markets and subject to review from 24 months after study completion. Such requests can be made to Moderna Inc., 325 Binney Street, Cambridge, MA 02142, [email protected].