Yue Rong, Zeng Fengyuan, Ma Danjing, Meng Ziyan, Li Xinghang, Zhang Zhenxiao, Zhang Haobo, Li Qi, Xu Langxi, Niu Zhenye, Li Dandan, Liao Yun, Jiang Guorun, Yu Li, Zhao Heng, Zhang Ying, Liu Longding, Li Qihan
Yunnan Key Laboratory of Vaccine Research and Development for Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medicine Sciences & Peking Union Medical College, Kunming 650118, China.
Vaccines (Basel). 2023 Feb 23;11(3):524. doi: 10.3390/vaccines11030524.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike (S) protein is a critical viral antigenic protein that enables the production of neutralizing antibodies, while other structural proteins, including the membrane (M), nucleocapsid (N) and envelope (E) proteins, have unclear roles in antiviral immunity. In this study, S1, S2, M, N and E proteins were expressed in 16HBE cells to explore the characteristics of the resultant innate immune response. Furthermore, peripheral blood mononuclear cells (PBMCs) from mice immunized with two doses of inactivated SARS-CoV-2 vaccine or two doses of mRNA vaccine were isolated and stimulated by these five proteins to evaluate the corresponding specific T-cell immune response. In addition, the levels of humoral immunity induced by two-dose inactivated vaccine priming followed by mRNA vaccine boosting, two homologous inactivated vaccine doses and two homologous mRNA vaccine doses in immunized mice were compared. Our results suggested that viral structural proteins can activate the innate immune response and elicit a specific T-cell response in mice immunized with the inactivated vaccine. However, the existence of the specific T-cell response against M, N and E is seemingly insufficient to improve the level of humoral immunity.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突（S）蛋白是一种关键的病毒抗原蛋白，可促使产生中和抗体，而其他结构蛋白，包括膜（M）、核衣壳（N）和包膜（E）蛋白，在抗病毒免疫中的作用尚不清楚。在本研究中，S1、S2、M、N和E蛋白在16HBE细胞中表达，以探索由此产生的固有免疫反应的特征。此外，分离用两剂灭活SARS-CoV-2疫苗或两剂mRNA疫苗免疫的小鼠的外周血单个核细胞（PBMC），并用这五种蛋白进行刺激，以评估相应的特异性T细胞免疫反应。此外，还比较了在免疫小鼠中，两剂灭活疫苗初免后用mRNA疫苗加强、两剂同源灭活疫苗和两剂同源mRNA疫苗诱导的体液免疫水平。我们的结果表明，病毒结构蛋白可激活固有免疫反应，并在接种灭活疫苗的小鼠中引发特异性T细胞反应。然而，针对M、N和E的特异性T细胞反应的存在似乎不足以提高体液免疫水平。
