Interferon mediated prophylactic protection against respiratory viruses conferred by a prototype live attenuated influenza virus vaccine lacking non-structural protein 1

The influenza A non-structural protein 1 (NS1) is known for its ability to hinder the synthesis of type I interferon (IFN) during viral infection. Influenza viruses lacking NS1 (Delta NS1) are under clinical development as live attenuated human influenza virus vaccines and induce potent influenza virus-specific humoral and cellular adaptive immune responses. Attenuation of Delta NS1 influenza viruses is due to their high IFN inducing properties, that limit their replication in vivo. This study demonstrates that pre-treatment with a Delta NS1 virus results in an antiviral state which prevents subsequent replication of homologous and heterologous viruses, preventing disease from virus respiratory pathogens, including SARS-CoV-2. Our studies suggest that Delta NS1 influenza viruses could be used for the prophylaxis of influenza, SARS-CoV-2 and other human respiratory viral infections, and that an influenza virus vaccine based on Delta NS1 live attenuated viruses would confer broad protection against influenza virus infection from the moment of administration, first by non-specific innate immune induction, followed by specific adaptive immunity.

Automated summary

The study shows that pre-treatment with Delta NS1 virus creates an antiviral state, preventing replication of homologous and heterologous viruses, thus preventing diseases caused by virus respiratory pathogens, including SARS-CoV-2. This suggests that Delta NS1 influenza viruses could be used for prophylaxis against influenza, SARS-CoV-2, and other human respiratory viral infections, and that a vaccine based on Delta NS1 live attenuated viruses would provide broad protection against influenza virus infection.