tetano
Editor, Senior Moderator
Nat Commun
. 2026 Apr 28.
doi: 10.1038/s41467-026-72426-4. Online ahead of print.
Generation of an autophagy-targeting influenza A virus as live attenuated vaccine
Jiawei Hao[SUP] #[/SUP][SUP] 1 [/SUP], Ping Wang[SUP] #[/SUP][SUP] 1 [/SUP], Le Li[SUP] 1 [/SUP], Qikai Wang[SUP] 1 [/SUP], Quan Shen[SUP] 1 2 [/SUP], Le Tong[SUP] 1 [/SUP], Chengyao Liu[SUP] 1 [/SUP], Zihao Wang[SUP] 1 [/SUP], Qisi Zhang[SUP] 1 [/SUP], Demin Zhou[SUP] 3 4 [/SUP], Xiaoshan Shi[SUP] 5 6 [/SUP], Longlong Si[SUP] 7 8 [/SUP]
Affiliations
Despite existing vaccines, influenza remains a significant public health burden, highlighting the need for vaccine strategies with improved safety and efficacy. Here we develop an autophagy-targeting influenza. A virus as a live attenuated vaccine by harnessing the host cell's autophagy machinery to manipulate viral protein degradation. The virus is generated by introducing a conditionally removable autophagosome-targeting motif in the viral genome, which enables viral attenuation through autophagy-mediated degradation of the tagged viral protein in conventional cells while permitting efficient viral replication for large-scale manufacturing in engineered cell lines. The engineered virus is highly attenuated in vivo but able to induce robust humoral, mucosal, and cellular immune responses, and provides complete cross-reactive protection against homologous and heterologous viral challenges. Together, this study establishes autophagy-mediated protein degradation as a viable strategy for tuning viral attenuation, which could be adapted for the rational design of live attenuated vaccines against additional pathogens.
. 2026 Apr 28.
doi: 10.1038/s41467-026-72426-4. Online ahead of print.
Generation of an autophagy-targeting influenza A virus as live attenuated vaccine
Jiawei Hao[SUP] #[/SUP][SUP] 1 [/SUP], Ping Wang[SUP] #[/SUP][SUP] 1 [/SUP], Le Li[SUP] 1 [/SUP], Qikai Wang[SUP] 1 [/SUP], Quan Shen[SUP] 1 2 [/SUP], Le Tong[SUP] 1 [/SUP], Chengyao Liu[SUP] 1 [/SUP], Zihao Wang[SUP] 1 [/SUP], Qisi Zhang[SUP] 1 [/SUP], Demin Zhou[SUP] 3 4 [/SUP], Xiaoshan Shi[SUP] 5 6 [/SUP], Longlong Si[SUP] 7 8 [/SUP]
Affiliations
- PMID: 42049736
- DOI: 10.1038/s41467-026-72426-4
Despite existing vaccines, influenza remains a significant public health burden, highlighting the need for vaccine strategies with improved safety and efficacy. Here we develop an autophagy-targeting influenza. A virus as a live attenuated vaccine by harnessing the host cell's autophagy machinery to manipulate viral protein degradation. The virus is generated by introducing a conditionally removable autophagosome-targeting motif in the viral genome, which enables viral attenuation through autophagy-mediated degradation of the tagged viral protein in conventional cells while permitting efficient viral replication for large-scale manufacturing in engineered cell lines. The engineered virus is highly attenuated in vivo but able to induce robust humoral, mucosal, and cellular immune responses, and provides complete cross-reactive protection against homologous and heterologous viral challenges. Together, this study establishes autophagy-mediated protein degradation as a viable strategy for tuning viral attenuation, which could be adapted for the rational design of live attenuated vaccines against additional pathogens.