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SARS-CoV-2 刺突蛋白的重组亚单位作为诱导中和抗体的疫苗候选物。

Recombinant subunits of SARS-CoV-2 spike protein as vaccine candidates to elicit neutralizing antibodies.

机构信息

Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Department of Biology Sciences, Shahid Rajaee Teacher Training University, Tehran, Iran.

出版信息

J Clin Lab Anal. 2022 May;36(5):e24328. doi: 10.1002/jcla.24328. Epub 2022 Mar 29.

DOI:10.1002/jcla.24328
PMID:35349744
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9102496/
Abstract

OBJECTIVES

The spike protein has been reported as one of the most critical targets for vaccine design strategies against the SARS-CoV-2 infection. Hence, we have designed, produced, and evaluated the potential use of three truncated recombinant proteins derived from spike protein as vaccine candidates capable of neutralizing SARS-CoV-2 virus.

METHODS

In silico tools were used to design spike-based subunit recombinant proteins (RBD (P ), fusion peptide (P ), and S1/S2 cleavage site (P )). These proteins were checked for their ability to be identified by the anti-SARS-CoV-2 antibodies by exposing them to COVID-19 serum samples. The proteins were also injected into mice and rabbit, and the antibody titers were measured for 390 days to assess their neutralization efficiency.

RESULTS

The antibodies that existed in the serum of COVID-19 patients were identified by designed proteins. The anti-spike antibody titer was increased in the animals injected with recombinant proteins. The VNT results revealed that the produced antibodies could neutralize the cultured live virus.

CONCLUSION

Truncated subunit vaccines could also be considered as robust tools for effective vaccination against COVID-19. Using a combination of in silico, in vitro, and in vivo experiments, it was shown that the injection of spike-based truncated recombinant proteins could stimulate long-lasting and neutralizing antibody responses.

摘要

目的

刺突蛋白已被报道为针对 SARS-CoV-2 感染的疫苗设计策略的最关键靶标之一。因此,我们设计、生产并评估了三种源自刺突蛋白的截短重组蛋白作为候选疫苗的潜在用途,这些疫苗能够中和 SARS-CoV-2 病毒。

方法

使用计算机工具设计基于刺突的亚单位重组蛋白(RBD(P)、融合肽(P)和 S1/S2 切割位点(P))。通过将这些蛋白暴露于 COVID-19 血清样本中来检查它们被抗 SARS-CoV-2 抗体识别的能力。还将这些蛋白注射到小鼠和兔子中,并测量 390 天的抗体滴度,以评估它们的中和效率。

结果

设计的蛋白可识别存在于 COVID-19 患者血清中的抗体。用重组蛋白注射的动物中,抗刺突抗体滴度增加。VNT 结果表明,产生的抗体可中和培养的活病毒。

结论

截短的亚单位疫苗也可被视为针对 COVID-19 有效接种的有效工具。通过使用计算机、体外和体内实验的组合,表明注射基于刺突的截短重组蛋白可以刺激持久和中和抗体反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf6/9102496/827667e96670/JCLA-36-e24328-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf6/9102496/2ca1cc34b362/JCLA-36-e24328-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf6/9102496/0faf2269a6c7/JCLA-36-e24328-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf6/9102496/1a11847da5b2/JCLA-36-e24328-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf6/9102496/827667e96670/JCLA-36-e24328-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf6/9102496/2ca1cc34b362/JCLA-36-e24328-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf6/9102496/0faf2269a6c7/JCLA-36-e24328-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf6/9102496/1a11847da5b2/JCLA-36-e24328-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf6/9102496/827667e96670/JCLA-36-e24328-g001.jpg

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