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基于重组 HEV-3 ORF2 衣壳蛋白的 SARS-CoV-2 病毒样颗粒的表达和免疫原性。

Expression and Immunogenicity of SARS-CoV-2 Virus-Like Particles based on Recombinant Truncated HEV-3 ORF2 Capsid Protein.

机构信息

National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin 130012, P.R. China.

School of Life Sciences, Jilin University, Changchun 130012, P.R. China.

出版信息

J Microbiol Biotechnol. 2022 Oct 28;32(10):1335-1343. doi: 10.4014/jmb.2205.05023. Epub 2022 Sep 19.

Abstract

COVID-19 is an emerging disease that poses a severe threat to global public health. As such, there is an urgent demand for vaccines against SARS-CoV-2, the virus that causes COVID-19. Here, we describe a virus-like nanoparticle candidate vaccine against SARS-CoV-2 produced by an expression system. The fusion protein of a truncated ORF2-encoded protein of aa 439~608 (p170) from hepatitis E virus CCJD-517 and the receptor-binding domain of the spike protein from SARS-CoV-2 were expressed, purified and characterized. The antigenicity and immunogenicity of p170-RBD were evaluated in vitro and in Kunming mice. Our investigation revealed that p170-RBD self-assembled into approximately 24 nm virus-like particles, which could bind to serum from vaccinated people ( < 0.001) and receptors on cells. Immunization with p170-RBD induced the titer of IgG antibody vaccine increased from 14 days post-immunization and was significantly enhanced after a booster immunization at 28 dpi, ultimately reaching a peak level on 42 dpi with a titer of 4.97 log. Pseudovirus neutralization tests showed that the candidate vaccine induced a strong neutralizing antibody response in mice. In this research, we demonstrated that p170-RBD possesses strong antigenicity and immunogenicity and could be a potential candidate for use in future SARS-CoV-2 vaccine development.

摘要

COVID-19 是一种新兴疾病,对全球公共卫生构成严重威胁。因此,人们迫切需要针对导致 COVID-19 的 SARS-CoV-2 病毒的疫苗。在这里,我们描述了一种由表达系统产生的针对 SARS-CoV-2 的病毒样纳米颗粒候选疫苗。表达、纯化和表征了来自丙型肝炎病毒 CCJD-517 的截短 ORF2 编码蛋白 aa439~608(p170)的融合蛋白和 SARS-CoV-2 的刺突蛋白的受体结合结构域。在体外和昆明小鼠中评估了 p170-RBD 的抗原性和免疫原性。我们的研究表明,p170-RBD 自组装成约 24nm 的病毒样颗粒,能够结合接种疫苗人群的血清(<0.001)和细胞上的受体。p170-RBD 免疫诱导 IgG 抗体疫苗滴度从免疫后 14 天开始增加,并在 28 天加强免疫后显著增强,最终在 42 天达到峰值,滴度为 4.97 对数。假病毒中和试验表明,候选疫苗在小鼠中诱导了强烈的中和抗体反应。在这项研究中,我们证明了 p170-RBD 具有很强的抗原性和免疫原性,可能成为未来 SARS-CoV-2 疫苗开发的潜在候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f84b/9668089/0342d5770124/jmb-32-10-1335-f1.jpg

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