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

IF 4.7 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2023-06-01 Epub Date: 2023-06-24 DOI:10.2217/fvl-2023-0066
Cao Minh Nguyen, Bac An Luong, Thu Thuy Thi Tran, Hoai Nghia Nguyen, Le Son Tran
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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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编码用于T细胞介导的免疫激活的严重急性呼吸系统综合征冠状病毒2型ORF1ab保守区的mRNA的设计和产生
目的:在严重急性呼吸系统综合征冠状病毒2型ORF1ab中产生编码保守区的信使核糖核酸,该信使核糖核酸可以诱导强烈的T细胞反应,以克服新出现的变异的免疫侵袭。方法:我们使用免疫信息学方法合成信使核糖核酸,选择了两个具有高密度T细胞表位的保守区域。通过ELISpot测定和流式细胞术检测mRNAs激活T细胞产生IFN-γ的能力。结果:在34名参与者中的29名参与者中,两种合成的mRNA在MDA-MB-231细胞中成功翻译,并具有与刺突mRNA相当的效力,在PBMC中诱导CD4+和CD8+T细胞反应。结论:本研究为利用严重急性呼吸系统综合征冠状病毒2型保守区开发能够引发T细胞介导免疫的加强疫苗提供了概念验证。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
期刊介绍: ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.
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