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<p>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.</p>

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Generation of an autophagy-targeting influenza A virus as live attenuated vaccine

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月28日

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  • Jiawei Hao,
  • Ping Wang,
  • Le Li,
  • Qikai Wang,
  • Quan Shen,
  • Le Tong,
  • Chengyao Liu,
  • Zihao Wang,
  • Qisi Zhang,
  • Demin Zhou,
  • Xiaoshan Shi,
  • Longlong Si

摘要

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.