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表达严重急性呼吸综合征冠状病毒2(SARS-CoV-2)刺突糖蛋白、S1或S2结构域的流感病毒样颗粒(VLP)疫苗

Influenza Virus-like Particle (VLP) Vaccines Expressing the SARS-CoV-2 S Glycoprotein, S1, or S2 Domains.

作者信息

Chu Ki-Back, Kang Hae-Ji, Yoon Keon-Woong, Lee Hae-Ahm, Moon Eun-Kyung, Han Beom-Ku, Quan Fu-Shi

机构信息

Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea.

Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea.

出版信息

Vaccines (Basel). 2021 Aug 18;9(8):920. doi: 10.3390/vaccines9080920.

Abstract

The ongoing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic had brought disastrous consequences throughout the entire world. While several manufactured vaccines have been approved for emergency use, continuous efforts to generate novel vaccines are needed. In this study, we developed SARS-CoV-2 virus-like particles (VLPs) containing the full length of spike (S) glycoprotein (S full), S1, or S2 together with the influenza matrix protein 1 (M1) as a core protein. Successfully constructed VLPs expressing the S full, S1, and S2 via Sf9 cell transfections were confirmed and characterized by Western blot and transmission electron microscopy (TEM). VLP immunization in mice induced higher levels of spike protein-specific IgG and its subclasses compared to naïve control, with IgG2a being the most predominant subclass. S full and S1 immune sera elicited virus-neutralizing activities, but these were not strong enough to fully inhibit receptor-ligand binding of the SARS-CoV-2. Neutralizing activities were not observed from the S2 VLP immune sera. Overall, our findings revealed that S full or S1 containing VLPs can be developed into effective vaccines.

摘要

持续的严重急性呼吸综合征冠状病毒2(SARS-CoV-2)大流行给全世界带来了灾难性后果。虽然几种已生产的疫苗已被批准用于紧急使用,但仍需要持续努力研发新型疫苗。在本研究中,我们开发了含有全长刺突(S)糖蛋白(S全长)、S1或S2以及流感基质蛋白1(M1)作为核心蛋白的SARS-CoV-2病毒样颗粒(VLP)。通过Sf9细胞转染成功构建的表达S全长、S1和S2的VLP通过蛋白质免疫印迹和透射电子显微镜(TEM)进行了确认和表征。与未免疫的对照相比,小鼠中的VLP免疫诱导了更高水平的刺突蛋白特异性IgG及其亚类,其中IgG2a是最主要的亚类。S全长和S1免疫血清引发了病毒中和活性,但这些活性不足以完全抑制SARS-CoV-2的受体-配体结合。从S2 VLP免疫血清中未观察到中和活性。总体而言,我们的研究结果表明,含有S全长或S1的VLP可以开发成有效的疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a35/8402567/e90a869ec434/vaccines-09-00920-g001a.jpg

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