TY - JOUR
T1 - Interferon mediated prophylactic protection against respiratory viruses conferred by a prototype live attenuated influenza virus vaccine lacking non-structural protein 1
AU - Rathnasinghe, Raveen
AU - Salvatore, Mirella
AU - Zheng, Hongyong
AU - Jangra, Sonia
AU - Kehrer, Thomas
AU - Mena, Ignacio
AU - Schotsaert, Michael
AU - Muster, Thomas
AU - Palese, Peter
AU - García-Sastre, Adolfo
N1 - Funding Information:
The authors acknowledge members of AG-S and PP laboratories for their critical discussions. Technical assistance for the study was provided by Louis Ngyenvu and Richard Cadagan. We thank R. Albrecht for support with the BSL3 facility and procedures at the Icahn School of Medicine at Mount Sinai, New York. A2G mice were kindly provided by Dr. Heinz Arnheiter (NIH). hvPR8 virus was a generous gift from Drs. Otto Haller (University of Freiburg) and Jerome L. Schulman (Icahn School of Medicine). Recombinant Chicken IFN was a gift from Drs. Peter Staeheli (University of Freiburg) and Bernd Kaspers (University of Munich). This work was partly supported by the Centre for on Research for Influenza Pathogenesis, a Center of Excellence for Influenza Research and Surveillance supported by the National Institute of Allergy and Infectious Diseases (contract number HHSN272201400008C), CRIPT (Center for Research on Influenza Pathogenesis and Transmission) a Center of Excellence for Influenza Research and Response (CEIRR, NIAID contract number 75N93021C00014) by the NIAID funded Collaborative Influenza Vaccine Innovation Centers (contract number 75N93019C00051), by NIAID grants R01AI141226, R01AI145870 and P01AI097092, by DARPA grant HR0011-19-2-0020, and by the generous support of the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611 (5384)), and anonymous donors to AG-S and PP.
Funding Information:
AG–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 García-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. The rest of the authors have no conflicts to declare.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
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 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.
AB - 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 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.
UR - http://www.scopus.com/inward/record.url?scp=85119000288&partnerID=8YFLogxK
U2 - 10.1038/s41598-021-01780-8
DO - 10.1038/s41598-021-01780-8
M3 - Article
C2 - 34773048
AN - SCOPUS:85119000288
SN - 2045-2322
VL - 11
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 22164
ER -