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<p>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.</p>

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Lysosome-targeting live attenuated influenza vaccines elicit robust and broad immunity in mice

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月18日

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  • Jiawei Hao,
  • Ping Wang,
  • Quan Shen,
  • Xuetong Xi,
  • Le Tong,
  • Jihuan Hou,
  • Le Li,
  • Qikai Wang,
  • Chengyao Liu,
  • Jing Li,
  • Huafang Zhao,
  • Qisi Zhang,
  • Roberto Plebani,
  • David Chou,
  • Lihe Zhang,
  • Demin Zhou,
  • Longlong Si

摘要

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.