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新型冠状病毒核衣壳蛋白是开发新一代疫苗的潜在靶点。

Nucleocapsid protein of SARS-CoV-2 is a potential target for developing new generation of vaccine.

机构信息

School of Basic Medical Science, Wenzhou Medical University, Wenzhou, China.

Department of Laboratory Medicine, The Sixth People Hospital of Wenzhou, Wenzhou, China.

出版信息

J Clin Lab Anal. 2022 Jun;36(6):e24479. doi: 10.1002/jcla.24479. Epub 2022 May 9.

Abstract

BACKGROUND

SARS-CoV-2 has spread worldwide causing more than 400 million people with virus infections since early 2020. Currently, the existing vaccines targeting the spike glycoprotein (S protein) of SARS-CoV-2 are facing great challenge from the infection of SARS-CoV-2 virus and its multiple S protein variants. Thus, we need to develop a new generation of vaccines to prevent infection of the SARS-CoV-2 variants. Compared with the S protein, the nucleocapsid protein (N protein) of SARS-CoV-2 is more conservative and less mutations, which also plays a vital role in viral infection. Therefore, the N protein may have the great potential for developing new vaccines.

METHODS

The N protein of SARS-CoV-2 was recombinantly expressed and purified in Escherichia coli. Western Blot and ELISA assays were used to demonstrate the immunoreactivity of the recombinant N protein with the serum of 22 COVID-19 patients. We investigated further the response of the specific serum antibodies and cytokine production in BALB/c mice immunized with recombinant N protein by Western Blot and ELISA.

RESULTS

The N protein had good immunoreactivity and the production of IgG antibody against N protein in COVID-19 patients was tightly correlated with disease severity. Furthermore, the N protein was used to immunize BALB/c mice to have elicited strong immune responses. Not only high levels of IgG antibody, but also cytokine-IFN-γ were produced in the N protein-immunized mice. Importantly, the N protein immunization induced a high level of IgM antibody produced in the mice.

CONCLUSION

SARS-CoV-2 N protein shows a great big bundle of potentiality for developing a new generation of vaccines in fighting infection of SARS-CoV-2 and its variants.

摘要

背景

自 2020 年初以来,SARS-CoV-2 已在全球范围内传播,导致超过 4 亿人感染该病毒。目前,针对 SARS-CoV-2 刺突糖蛋白(S 蛋白)的现有疫苗正面临来自 SARS-CoV-2 病毒及其多种 S 蛋白变异体感染的巨大挑战。因此,我们需要开发新一代疫苗来预防 SARS-CoV-2 变异体的感染。与 S 蛋白相比,SARS-CoV-2 的核衣壳蛋白(N 蛋白)更为保守,突变较少,在病毒感染中也起着至关重要的作用。因此,N 蛋白可能具有开发新型疫苗的巨大潜力。

方法

在大肠杆菌中重组表达和纯化 SARS-CoV-2 的 N 蛋白。Western Blot 和 ELISA 检测用于证明重组 N 蛋白与 22 例 COVID-19 患者血清的免疫反应性。我们通过 Western Blot 和 ELISA 进一步研究了重组 N 蛋白免疫 BALB/c 小鼠后特异性血清抗体的反应和细胞因子的产生。

结果

N 蛋白具有良好的免疫反应性,COVID-19 患者针对 N 蛋白的 IgG 抗体的产生与疾病严重程度密切相关。此外,N 蛋白用于免疫 BALB/c 小鼠可引起强烈的免疫反应。N 蛋白免疫小鼠不仅产生高水平的 IgG 抗体,还产生细胞因子 IFN-γ。重要的是,N 蛋白免疫诱导小鼠产生高水平的 IgM 抗体。

结论

SARS-CoV-2 N 蛋白在开发新一代疫苗以对抗 SARS-CoV-2 及其变异体感染方面显示出巨大的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3409/9169192/bbdbe51717d1/JCLA-36-e24479-g007.jpg

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