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

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. Influenza virus infection is a global health threat and vaccines are required that show broad protection against a range of viral subtypes. Here the authors present a universal influenza vaccine based on Escherichia coli Nissle 1917 that activates innate and adaptive humoral and mucosal immunity, providing both immediate and long-term protection against influenza A virus infection in a murine model.