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科学家利用蛋白水解靶向开发出甲型流感减毒活疫苗
作者:小柯机器人 发布时间:2022/7/8 14:01:15

中国科学院深圳先进技术研究院司龙龙等研究人员利用蛋白水解靶向开发出甲型流感减毒活疫苗。相关论文于2022年7月4日在线发表在《自然—生物技术》杂志上。

研究人员描述了利用蛋白分解靶向嵌合体(PROTAC)技术产生的减毒活体甲型流感病毒疫苗,通过宿主细胞的内源性泛素-蛋白酶体系统降解病毒蛋白。研究人员在为病毒生产而设计的稳定细胞系中设计了甲型流感病毒的基因组,引入了一个可有条件去除的蛋白酶体靶向结构域,从而产生了完全感染性的PROTAC病毒,在感染后被宿主蛋白降解机制活体减毒。
 
在小鼠和雪貂模型中,PROTAC病毒被高度减弱,并能引起强大而广泛的体液、粘膜和细胞免疫,来应对同源和异源病毒的感染。PROTAC介导的病毒减弱可能广泛适用于生成减毒活疫苗。
 
据介绍,减毒活疫苗的实用性一直受限于不理想的免疫原性、安全问题或繁琐的制造过程和技术。
 
附:英文原文

Title: Generation of a live attenuated influenza A vaccine by proteolysis targeting

Author: Si, Longlong, Shen, Quan, Li, Jing, Chen, Li, Shen, Jinying, Xiao, Xue, Bai, Haiqing, Feng, Tang, Ye, Adam Yongxin, Li, Le, Zhang, Chunhe, Li, Zhen, Wang, Ping, Oh, Crystal Yuri, Nurani, Atiq, Niu, Siwen, Zhang, Chengxin, Wei, Xiaoqiong, Yuan, Wanqiong, Liao, Hao, Huang, Xiaojie, Wang, Ning, Tian, Wen-xia, Tian, Hongwei, Li, Li, Liu, Xiaoheng, Plebani, Roberto

Issue&Volume: 2022-07-04

Abstract: The usefulness of live attenuated virus vaccines has been limited by suboptimal immunogenicity, safety concerns or cumbersome manufacturing processes and techniques. Here we describe the generation of a live attenuated influenza A virus vaccine using proteolysis-targeting chimeric (PROTAC) technology to degrade viral proteins via the endogenous ubiquitin–proteasome system of host cells. We engineered the genome of influenza A viruses in stable cell lines engineered for virus production to introduce a conditionally removable proteasome-targeting domain, generating fully infective PROTAC viruses that were live attenuated by the host protein degradation machinery upon infection. In mouse and ferret models, PROTAC viruses were highly attenuated and able to elicit robust and broad humoral, mucosal and cellular immunity against homologous and heterologous virus challenges. PROTAC-mediated attenuation of viruses may be broadly applicable for generating live attenuated vaccines. Influenza virus is attenuated for vaccine production using PROTAC degradation technology.

DOI: 10.1038/s41587-022-01381-4

Source: https://www.nature.com/articles/s41587-022-01381-4

期刊信息

Nature Biotechnology:《自然—生物技术》,创刊于1996年。隶属于施普林格·自然出版集团,最新IF:31.864
官方网址:https://www.nature.com/nbt/
投稿链接:https://mts-nbt.nature.com/cgi-bin/main.plex