Design and generation of mRNAs encoding conserved regions of SARS-CoV-2 ORF1ab for T cell-mediated immune activation

设计和生成编码SARS-CoV-2 ORF1ab保守区域的mRNA,用于T细胞介导的免疫激活

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作者:Cao Minh Nguyen ,Bac An Luong ,Thu Thuy Thi Tran ,Hoai Nghia Nguyen ,Le Son Tran

Abstract

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.

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