tetano
Editor, Senior Moderator
Nat Commun
. 2026 Mar 18;17(1):2021.
doi: 10.1038/s41467-026-69920-0.
Lysosome-targeting live attenuated influenza vaccines elicit robust and broad immunity in mice
Jiawei Hao[SUP] 1 [/SUP], Ping Wang[SUP] 1 [/SUP], Quan Shen[SUP] 1 2 [/SUP], Xuetong Xi[SUP] 1 2 [/SUP], Le Tong[SUP] 1 [/SUP], Jihuan Hou[SUP] 1 [/SUP], Le Li[SUP] 1 [/SUP], Qikai Wang[SUP] 1 [/SUP], Chengyao Liu[SUP] 1 [/SUP], Jing Li[SUP] 1 [/SUP], Huafang Zhao[SUP] 1 [/SUP], Qisi Zhang[SUP] 1 [/SUP], Roberto Plebani[SUP] 3 [/SUP], David Chou[SUP] 4 [/SUP], Lihe Zhang[SUP] 5 [/SUP], Demin Zhou[SUP] 5 6 [/SUP], Longlong Si[SUP] 7 8 [/SUP]
Affiliations
The lysosome is a cell's endogenous machinery responsible for degrading proteins. Here we describe two lysosome-targeting live attenuated vaccine approaches, LYTAR 1.0 and LYTAR 2.0, by harnessing the lysosome to conditionally degrade viral proteins of influenza virus. LYTAR 1.0 incorporates a conditionally removable lysosome-targeting motif at the N- or C-terminus of viral proteins. LYTAR 2.0 allows flexible placement of lysosome-targeting motifs at internal or terminal sites of viral proteins. The resulting lysosome-targeting vaccine strains are attenuated by lysosome-mediated viral protein degradation in conventional cells, while maintaining replication efficiencies comparable to the wild-type virus in producer cell lines. In mouse models, these vaccine candidates are attenuated, induce strong and broad adaptive immune responses, and provide cross-reactive protection against H1N1 and H3N2 influenza viral challenges. This study establishes a lysosome-targeting vaccine platform for developing safe and effective live attenuated vaccines.
. 2026 Mar 18;17(1):2021.
doi: 10.1038/s41467-026-69920-0.
Lysosome-targeting live attenuated influenza vaccines elicit robust and broad immunity in mice
Jiawei Hao[SUP] 1 [/SUP], Ping Wang[SUP] 1 [/SUP], Quan Shen[SUP] 1 2 [/SUP], Xuetong Xi[SUP] 1 2 [/SUP], Le Tong[SUP] 1 [/SUP], Jihuan Hou[SUP] 1 [/SUP], Le Li[SUP] 1 [/SUP], Qikai Wang[SUP] 1 [/SUP], Chengyao Liu[SUP] 1 [/SUP], Jing Li[SUP] 1 [/SUP], Huafang Zhao[SUP] 1 [/SUP], Qisi Zhang[SUP] 1 [/SUP], Roberto Plebani[SUP] 3 [/SUP], David Chou[SUP] 4 [/SUP], Lihe Zhang[SUP] 5 [/SUP], Demin Zhou[SUP] 5 6 [/SUP], Longlong Si[SUP] 7 8 [/SUP]
Affiliations
- PMID: 41851138
- PMCID: PMC12999990
- DOI: 10.1038/s41467-026-69920-0
The lysosome is a cell's endogenous machinery responsible for degrading proteins. Here we describe two lysosome-targeting live attenuated vaccine approaches, LYTAR 1.0 and LYTAR 2.0, by harnessing the lysosome to conditionally degrade viral proteins of influenza virus. LYTAR 1.0 incorporates a conditionally removable lysosome-targeting motif at the N- or C-terminus of viral proteins. LYTAR 2.0 allows flexible placement of lysosome-targeting motifs at internal or terminal sites of viral proteins. The resulting lysosome-targeting vaccine strains are attenuated by lysosome-mediated viral protein degradation in conventional cells, while maintaining replication efficiencies comparable to the wild-type virus in producer cell lines. In mouse models, these vaccine candidates are attenuated, induce strong and broad adaptive immune responses, and provide cross-reactive protection against H1N1 and H3N2 influenza viral challenges. This study establishes a lysosome-targeting vaccine platform for developing safe and effective live attenuated vaccines.