TY - JOUR T1 - Prophylactic protection against respiratory viruses conferred by a prototype live attenuated influenza virus vaccine JF - bioRxiv DO - 10.1101/2021.04.28.441797 SP - 2021.04.28.441797 AU - Raveen Rathnasinghe AU - Mirella Salvatore AU - Hongyong Zheng AU - Sonia Jangra AU - Thomas Kehrer AU - Ignacio Mena AU - Michael Schotsaert AU - Thomas Muster AU - Peter Palese AU - Adolfo García-Sastre Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/04/28/2021.04.28.441797.abstract N2 - 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 (ΔNS1) 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 ΔNS1 influenza viruses is due to their high IFN inducing properties, that limit their replication in vivo. This study demonstrates that pre-treatment with a ΔNS1 virus results in an immediate 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 ΔNS1 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 ΔNS1 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.Competing Interest StatementAG-S and PP are inventors in patents owned by the Icahn School of Medicine and licensed to Vivaldi Biosciences concerning the use of NS1 deficient viruses as human vaccines and to BI Vetmedica on the use of NS1 deficient viruses as veterinarian vaccines. The Garcia-Sastre Laboratory has received research support from Pfizer, Senhwa Biosciences, 7Hills Pharma, Pharmamar, Blade Therapeutics, Avimex, Accurius, Dynavax, Kenall Manufacturing, ImmunityBio and Nanocomposix; and A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Vivaldi Biosciences, Pagoda, Contrafect, Vaxalto, Accurius, 7Hills Pharma, Avimex, Esperovax and Farmak. ER -