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Abstract：
Influenza virus is attenuated for vaccine production using PROTAC degradation technology. 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.
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NATURE BIOTECHNOLOGY
ISSN： 1087-0156
Year： 2022
Issue： 9
Volume： 40
Page： 1370-+
5 4 . 9 0 8
JCR@2020
ESI Discipline： BIOLOGY & BIOCHEMISTRY;
ESI HC Threshold：6
Cited Count：
SCOPUS Cited Count： 22
ESI Highly Cited Papers on the List： 0 Unfold All
WanFang Cited Count：
Chinese Cited Count：
30 Days PV： 1
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