文献类型： 外文期刊

第一作者： Shang, Yu

作者： Shang, Yu;Li, Li;Zhang, Tengfei;Luo, Qingping;Zeng, Zhe;Li, Lintao;Jia, Miaomiao;Tang, Guoyi;Fan, Sanlin;Lu, Qin;Zhang, Wenting;Xue, Yuhan;Wang, Hongling;Liu, Wei;Wang, Hongcai;Zhang, Rongrong;Shao, Huabin;Wen, Guoyuan;Shang, Yu;Li, Li;Zhang, Tengfei;Luo, Qingping;Zeng, Zhe;Li, Lintao;Jia, Miaomiao;Tang, Guoyi;Fan, Sanlin;Lu, Qin;Zhang, Wenting;Xue, Yuhan;Wang, Hongling;Liu, Wei;Wang, Hongcai;Zhang, Rongrong;Shao, Huabin;Wen, Guoyuan;Yu, Qingzhong;Ding, Chan;Shao, Huabin;Wen, Guoyuan

作者机构：

期刊名称：PLOS PATHOGENS （ 影响因子：7.464； 五年影响因子：7.913 ）

ISSN： 1553-7366

年卷期： 2022 年 18 卷 6 期

页码：

收录情况： SCI

摘要： Author summaryThe development of thermal stable vaccines can assist in the execution and expansion of global immunization programs, due to their decreased dependence on the cold chain for transport and storage. Research into the mechanism of viral thermostability may provide strategies for developing thermal stable vaccines. However, the mechanism by which an enveloped virus inherits its thermostability is poorly understood. Previously, we identified that the attachment glycoprotein (hemagglutinin-neuraminidase, HN) was responsible for the thermostability of Newcastle disease virus (NDV). In the present study, we further demonstrated that negative surface charge of HN protein positively regulated the thermostability of NDV through preventing the aggregation of HN protein. By genetically engineering charge-associated amino acid mutations onto the surface of the attachment glycoprotein of an enveloped virus vaccine strain, we remarkably improved the NDV and influenza virus vaccine's thermal stability and potency. Based on these data, we proposed a novel surface-charge-mediated link between HN protein and NDV thermostability, and provided a novel strategy for rational design of thermal stable enveloped virus vaccines. The development of thermostable vaccines can relieve the bottleneck of existing vaccines caused by thermal instability and subsequent poor efficacy, which is one of the predominant reasons for the millions of deaths caused by vaccine-preventable diseases. Research into the mechanism of viral thermostability may provide strategies for developing thermostable vaccines. Using Newcastle disease virus (NDV) as model, we identified the negative surface charge of attachment glycoprotein as a novel determinant of viral thermostability. It prevented the temperature-induced aggregation of glycoprotein and subsequent detachment from virion surface. Then structural stability of virion surface was improved and virus could bind to and infect cells efficiently after heat-treatment. Employing the approach of surface charge engineering, thermal stability of NDV and influenza A virus (IAV) vaccines was successfully improved. The increase in the level of vaccine thermal stability was determined by the value-added in the negative surface charge of the attachment glycoprotein. The engineered live and inactivated vaccines could be used efficiently after storage at 37 degrees C for at least 10 and 60 days, respectively. Thus, our results revealed a novel surface-charge-mediated link between HN protein and NDV thermostability, which could be used to design thermal stable NDV and IAV vaccines rationally.

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