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表达包膜和膜蛋白的 DNA 疫苗为小鼠提供针对 SARS-CoV-2 的部分保护。

DNA Vaccines Expressing the Envelope and Membrane Proteins Provide Partial Protection Against SARS-CoV-2 in Mice.

机构信息

School of Public Health, Xinxiang Medical University, Xinxiang, China.

National Health Commission (NHC) Key Laboratory of Medical Virology, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.

出版信息

Front Immunol. 2022 Feb 24;13:827605. doi: 10.3389/fimmu.2022.827605. eCollection 2022.

Abstract

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a public health emergency of international concern, and an effective vaccine is urgently needed to control the pandemic. Envelope (E) and membrane (M) proteins are highly conserved structural proteins among SARS-CoV-2 and SARS-CoV and have been proposed as potential targets for the development of cross-protective vaccines. Here, synthetic DNA vaccines encoding SARS-CoV-2 E/M proteins (called p-SARS-CoV-2-E/M) were developed, and mice were immunised with three doses intramuscular injection and electroporation. Significant cellular immune responses were elicited, whereas no robust humoral immunity was detected. In addition, novel H-2d-restricted T-cell epitopes were identified. Notably, although no drop in lung tissue virus titre was detected in DNA-vaccinated mice post-challenge with SARS-CoV-2, immunisation with either p-SARS-CoV-2-E or p-SARS-CoV-2-M provided minor protection and co-immunisation with p-SARS-CoV-2-E+M increased protection. Therefore, E/M proteins should be considered as vaccine candidates as they may be valuable in the optimisation of vaccination strategies against COVID-19.

摘要

新型冠状病毒病 2019(COVID-19)由严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)引起,已成为国际关注的公共卫生突发事件,急需有效的疫苗来控制疫情。包膜(E)和膜(M)蛋白是 SARS-CoV-2 和 SARS-CoV 中高度保守的结构蛋白,被提议作为开发交叉保护疫苗的潜在靶点。在这里,我们开发了编码 SARS-CoV-2 E/M 蛋白的合成 DNA 疫苗(称为 p-SARS-CoV-2-E/M),并用三种剂量经肌肉内注射和电穿孔免疫小鼠。结果引发了显著的细胞免疫反应,而没有检测到强大的体液免疫反应。此外,还鉴定了新的 H-2d 限制性 T 细胞表位。值得注意的是,尽管在 SARS-CoV-2 攻毒后 DNA 疫苗接种的小鼠肺组织病毒滴度没有下降,但接种 p-SARS-CoV-2-E 或 p-SARS-CoV-2-M 均可提供轻微保护,而 p-SARS-CoV-2-E+M 的联合免疫可增加保护作用。因此,E/M 蛋白可被视为疫苗候选物,因为它们可能有助于优化针对 COVID-19 的疫苗接种策略。

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