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单克隆抗体靶向 H1N1 流感病毒的 HA191/199 区域介导神经细胞损伤。

Monoclonal Antibody Targeting the HA191/199 Region of H1N1 Influenza Virus Mediates the Damage of Neural Cells.

机构信息

Central Laboratory of Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, 710068, China.

Shaanxi Province Research Center of Cell Immunological Engineering and Technology, Xi'an, Shaanxi, 710068, China.

出版信息

Biochemistry (Mosc). 2021 Nov;86(11):1469-1476. doi: 10.1134/S0006297921110109.

Abstract

Vaccination is the most effective mean of preventing influenza virus infections. However, vaccination-induced adverse reactions of the nervous system, the causes of which are unknown, lead to concerns on the safety of influenza A vaccine. In this study, we used flow cytometry, cell ELISA, and immunofluorescence to find that H1-84 monoclonal antibody (mAb) against the191/199 region of the H1N1 influenza virus hemagglutinin (HA) protein binds to neural cells and mediates cell damage. Using molecular simulation software, such as PyMOL and PDB viewer, we demonstrated that the HA191/199 region maintains the overall structure of the HA head. Since the HA191/199 region cannot be removed from the HA structure, it has to be altered via introducing point mutations by site-directed mutagenesis. This will provide an innovative theoretical support for the subsequent modification the influenza A vaccine for increasing its safety.

摘要

接种疫苗是预防流感病毒感染最有效的手段。然而,接种疫苗后会引起神经系统不良反应,其原因尚不清楚,这引起了人们对甲型流感疫苗安全性的担忧。在这项研究中,我们使用流式细胞术、细胞酶联免疫吸附试验和免疫荧光法发现,针对甲型 H1N1 流感病毒血凝素(HA)蛋白 191/199 区域的 H1-84 单克隆抗体(mAb)与神经细胞结合并介导细胞损伤。使用分子模拟软件,如 PyMOL 和 PDB viewer,我们证明了 HA191/199 区域维持了 HA 头部的整体结构。由于 HA191/199 区域不能从 HA 结构中去除,因此必须通过定点突变引入点突变来改变它。这将为后续改进甲型流感疫苗以提高其安全性提供创新性的理论支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8518/8588936/e9282cd7c54f/10541_2021_2252_Fig1_HTML.jpg

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