tetano
Editor, Senior Moderator
Nat Microbiol
. 2025 Jan 15.
doi: 10.1038/s41564-024-01908-2. Online ahead of print. Proteolysis-targeting influenza vaccine strains induce broad-spectrum immunity and in vivo protection
Jinying Shen[SUP] #[/SUP][SUP] 1 [/SUP], Jing Li[SUP] #[/SUP][SUP] 1 [/SUP], Quan Shen[SUP] #[/SUP][SUP] 1 2 [/SUP], Jihuan Hou[SUP] #[/SUP][SUP] 1 [/SUP], Chunhe Zhang[SUP] #[/SUP][SUP] 1 [/SUP], Haiqing Bai[SUP] #[/SUP][SUP] 3 4 [/SUP], Xiaoni Ai[SUP] #[/SUP][SUP] 5 [/SUP], Yinlei Su[SUP] 1 [/SUP], Zihao Wang[SUP] 1 [/SUP], Yunfei Zhang[SUP] 1 [/SUP], Beibei Xu[SUP] 1 [/SUP], Jiawei Hao[SUP] 1 [/SUP], Ping Wang[SUP] 1 [/SUP], Qisi Zhang[SUP] 1 [/SUP], Adam Yongxin Ye[SUP] 6 [/SUP], Zhen Li[SUP] 1 7 [/SUP], Tang Feng[SUP] 8 [/SUP], Le Li[SUP] 1 [/SUP], Fei Qi[SUP] 1 [/SUP], Qikai Wang[SUP] 1 [/SUP], Yacong Sun[SUP] 1 [/SUP], Chengyao Liu[SUP] 1 [/SUP], Xuetong Xi[SUP] 1 2 [/SUP], Lei Yan[SUP] 9 [/SUP], Hanhui Hong[SUP] 10 [/SUP], Yuting Chen[SUP] 1 [/SUP], Xin Xie[SUP] 3 4 [/SUP], Jing Xie[SUP] 8 11 [/SUP], Xiaoheng Liu[SUP] 11 [/SUP], Ruikun Du[SUP] 12 [/SUP], Roberto Plebani[SUP] 13 [/SUP], Lihe Zhang[SUP] 5 [/SUP], Demin Zhou[SUP] 5 7 [/SUP], George Church[SUP] 6 [/SUP], Longlong Si[SUP] 14 15 [/SUP]
Affiliations
Generating effective live vaccines from intact viruses remains challenging owing to considerations of safety and immunogenicity. Approaches that can be applied in a systematic manner are needed. Here we created a library of live attenuated influenza vaccines by using diverse cellular E3 ubiquitin ligases to generate proteolysis-targeting (PROTAR) influenza A viruses. PROTAR viruses were engineered to be attenuated by the ubiquitin-proteasome system, which mediates viral protein degradation in conventional host cells, but allows efficient replication in engineered cell lines for large-scale manufacturing. Depending on the degron-E3 ligase pairs, viruses showed varying degrees of attenuation. In animal models, PROTAR viruses were highly attenuated and elicited robust, broad, strain-dependent humoral, mucosal and cellular immunity. In addition, they provided cross-reactive protection against homologous and heterologous viral challenges. This study provides a systematic approach for developing safe and effective vaccines, with potential applications in designing live attenuated vaccines against other pathogens.
. 2025 Jan 15.
doi: 10.1038/s41564-024-01908-2. Online ahead of print. Proteolysis-targeting influenza vaccine strains induce broad-spectrum immunity and in vivo protection
Jinying Shen[SUP] #[/SUP][SUP] 1 [/SUP], Jing Li[SUP] #[/SUP][SUP] 1 [/SUP], Quan Shen[SUP] #[/SUP][SUP] 1 2 [/SUP], Jihuan Hou[SUP] #[/SUP][SUP] 1 [/SUP], Chunhe Zhang[SUP] #[/SUP][SUP] 1 [/SUP], Haiqing Bai[SUP] #[/SUP][SUP] 3 4 [/SUP], Xiaoni Ai[SUP] #[/SUP][SUP] 5 [/SUP], Yinlei Su[SUP] 1 [/SUP], Zihao Wang[SUP] 1 [/SUP], Yunfei Zhang[SUP] 1 [/SUP], Beibei Xu[SUP] 1 [/SUP], Jiawei Hao[SUP] 1 [/SUP], Ping Wang[SUP] 1 [/SUP], Qisi Zhang[SUP] 1 [/SUP], Adam Yongxin Ye[SUP] 6 [/SUP], Zhen Li[SUP] 1 7 [/SUP], Tang Feng[SUP] 8 [/SUP], Le Li[SUP] 1 [/SUP], Fei Qi[SUP] 1 [/SUP], Qikai Wang[SUP] 1 [/SUP], Yacong Sun[SUP] 1 [/SUP], Chengyao Liu[SUP] 1 [/SUP], Xuetong Xi[SUP] 1 2 [/SUP], Lei Yan[SUP] 9 [/SUP], Hanhui Hong[SUP] 10 [/SUP], Yuting Chen[SUP] 1 [/SUP], Xin Xie[SUP] 3 4 [/SUP], Jing Xie[SUP] 8 11 [/SUP], Xiaoheng Liu[SUP] 11 [/SUP], Ruikun Du[SUP] 12 [/SUP], Roberto Plebani[SUP] 13 [/SUP], Lihe Zhang[SUP] 5 [/SUP], Demin Zhou[SUP] 5 7 [/SUP], George Church[SUP] 6 [/SUP], Longlong Si[SUP] 14 15 [/SUP]
Affiliations
- PMID: 39815008
- DOI: 10.1038/s41564-024-01908-2
Generating effective live vaccines from intact viruses remains challenging owing to considerations of safety and immunogenicity. Approaches that can be applied in a systematic manner are needed. Here we created a library of live attenuated influenza vaccines by using diverse cellular E3 ubiquitin ligases to generate proteolysis-targeting (PROTAR) influenza A viruses. PROTAR viruses were engineered to be attenuated by the ubiquitin-proteasome system, which mediates viral protein degradation in conventional host cells, but allows efficient replication in engineered cell lines for large-scale manufacturing. Depending on the degron-E3 ligase pairs, viruses showed varying degrees of attenuation. In animal models, PROTAR viruses were highly attenuated and elicited robust, broad, strain-dependent humoral, mucosal and cellular immunity. In addition, they provided cross-reactive protection against homologous and heterologous viral challenges. This study provides a systematic approach for developing safe and effective vaccines, with potential applications in designing live attenuated vaccines against other pathogens.