Aim: To generate mRNAs encoding conserved regions within SARS-CoV-2 ORF1ab which can induce strong T-cell responses to overcome the immune invasion of newly emergent variants.
Methods: We selected two conserved regions with a high density of T-cell epitopes using immunoinformatics for mRNA synthesis. The ability of testing mRNAs to activate T cells for IFN-γ production was examined by an ELISpot assay and flow cytometry.
Results: Two synthesized mRNAs were successfully translated in MDA-MB-231 cells and had comparable potency to the spike mRNA to induce CD4+ and CD8+ T-cell responses in peripheral blood mononuclear cells in 29 out of 34 participants.
Conclusion: This study provides a proof-of-concept for the use of SARS-CoV-2 conserved regions to develop booster vaccines capable of eliciting T-cell-mediated immunity.
Keywords: IFN-γ; ORF1ab; SARS-CoV-2; T cell epitopes; in vitro transcription (IVT); mRNA vaccine; peripheral blood mononuclear cells (PBMCs).
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