Engineered probiotic Escherichia coli elicits immediate and long-term protection against influenza A virus in mice

Ling Huang, Wei Tang, Lina He, Mengke Li, Xian Lin, Ao Hu, Xindi Huang, Zhouyu Wu, Zhiyong Wu, Shiyun Chen () and Yangbo Hu ()
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Ling Huang: Wuhan Institute of Virology, Chinese Academy of Sciences
Wei Tang: Wuhan Institute of Virology, Chinese Academy of Sciences
Lina He: Wuhan Institute of Virology, Chinese Academy of Sciences
Mengke Li: Wuhan Institute of Virology, Chinese Academy of Sciences
Xian Lin: Wuhan Institute of Virology, Chinese Academy of Sciences
Ao Hu: Wuhan Institute of Virology, Chinese Academy of Sciences
Xindi Huang: Wuhan Institute of Virology, Chinese Academy of Sciences
Zhouyu Wu: Wuhan Institute of Virology, Chinese Academy of Sciences
Zhiyong Wu: Wuhan Institute of Virology, Chinese Academy of Sciences
Shiyun Chen: Wuhan Institute of Virology, Chinese Academy of Sciences
Yangbo Hu: Wuhan Institute of Virology, Chinese Academy of Sciences

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Influenza virus infection remains a major global health problem and requires a universal vaccine with broad protection against different subtypes as well as a rapid-response vaccine to provide immediate protection in the event of an epidemic outbreak. Here, we show that intranasal administration of probiotic Escherichia coli Nissle 1917 activates innate immunity in the respiratory tract and provides immediate protection against influenza virus infection within 1 day. Based on this vehicle, a recombinant strain is engineered to express and secret five tandem repeats of the extracellular domain of matrix protein 2 from different influenza virus subtypes. Intranasal vaccination with this strain induces durable humoral and mucosal responses in the respiratory tract, and provides broad protection against the lethal challenge of divergent influenza viruses in female BALB/c mice. Our findings highlight a promising delivery platform for developing mucosal vaccines that provide immediate and sustained protection against respiratory pathogens.

Date: 2024
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DOI: 10.1038/s41467-024-51182-3

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