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Generation of a live attenuated influenza A vaccine by proteolysis targeting

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

in 631/1647/334/2247 / 631/250/590/1867 / 631/326/590/1867 / 631/61/51/1868 / 631/61/54/1866 / Agriculture / Animal models / Attenuation / Biodegradation / Bioinformatics / Biomedical and Life Sciences / Biomedical Engineering/Biotechnology / Biomedicine / Biotechnology / Cell lines / Cell-mediated immunity / Degradation / Engineering / Genomes / Homology / Hospitals / Humoral immunity / Immunogenicity / Infections / Influenza / Influenza A / Laboratories / Life Sciences / Manufacturing industry / Medicine / Mucosa / Mucosal immunity / Peptides / Proteasomes / Proteins / Proteolysis / Research centers / Technology utilization / Ubiquitin / Vaccines / Viral infections / Viruses

2022

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2022

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2022

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Journal Article

Generation of a live attenuated influenza A vaccine by proteolysis targeting

Li, Zhen,

Oh, Crystal Yuri,

Yuan, Wanqiong,

Chen, Li,

Si, Longlong,

Xiao, Xue,

Liao, Hao,

Shen, Quan,

Bai, Haiqing,

Plebani, Roberto,

Zhang, Chunhe,

Li, Li,

Feng, Tang,

Li, Le,

Tian, Hongwei,

Wang, Ning,

Li, Jing,

Wang, Ping,

Huang, Xiaojie,

Nurani, Atiq,

Niu, Siwen,

Tian, Wen-xia,

Ye, Adam Yongxin,

Zhang, Chengxin,

Shen, Jinying,

Wei, Xiaoqiong,

Liu, Xiaoheng

2022

Overview

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.

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Nature Publishing Group US,Nature Publishing Group

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