Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, 650031, China.
Yunnan University, Kunming, 650091, China.
J Nanobiotechnology. 2022 Jun 7;20(1):260. doi: 10.1186/s12951-022-01469-8.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), seriously threatens human life and health. The correct folding and polymerization of the receptor-binding domain (RBD) protein of coronavirus in Escherichia coli may reduce the cost of SARS-CoV-2 vaccines. In this study, we constructed this nanopore by using the principle of ClyA porin polymerization triggered by the cell membrane. We used surfactants to "pick" the ClyA-RBD nanopore from the bacterial outer membrane. More importantly, the polymerized RBD displayed on the ClyA-RBD polymerized porin (RBD-PP) already displays some correct spatial conformational epitopes that can induce neutralizing antibodies. The nanostructures of RBD-PP can target lymph nodes and promote antigen uptake and processing by dendritic cells, thereby effectively eliciting the production of anti-SARS-CoV-2 neutralizing antibodies, systemic cellular immune responses, and memory T cells. We applied this PP-based vaccine platform to fabricate an RBD-based subunit vaccine against SARS-CoV-2, which will provide a foundation for the development of inexpensive coronavirus vaccines. The development of a novel vaccine delivery system is an important part of innovative drug research. This novel PP-based vaccine platform is likely to have additional applications, including other viral vaccines, bacterial vaccines, tumor vaccines, drug delivery, and disease diagnosis.
新型冠状病毒病(COVID-19)由严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)引起,严重威胁人类的生命和健康。正确折叠和聚合冠状病毒的受体结合域(RBD)蛋白,可能会降低 SARS-CoV-2 疫苗的成本。在本研究中,我们利用细胞膜触发 ClyA 孔蛋白聚合的原理构建了这种纳米孔。我们使用表面活性剂从细菌外膜中“提取”ClyA-RBD 纳米孔。更重要的是,聚合的 RBD 展示在 ClyA-RBD 聚合孔蛋白(RBD-PP)上,已经显示出一些可以诱导中和抗体的正确空间构象表位。RBD-PP 的纳米结构可以靶向淋巴结,促进树突状细胞摄取和处理抗原,从而有效地引发抗 SARS-CoV-2 中和抗体、全身性细胞免疫反应和记忆 T 细胞的产生。我们将这种基于 PP 的疫苗平台应用于制造针对 SARS-CoV-2 的基于 RBD 的亚单位疫苗,为开发廉价的冠状病毒疫苗提供了基础。新型疫苗输送系统的开发是创新药物研究的重要组成部分。这种新型基于 PP 的疫苗平台可能具有其他应用,包括其他病毒疫苗、细菌疫苗、肿瘤疫苗、药物输送和疾病诊断。