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bioRxiv · 10.1101/2021.04.28.441797

Prophylactic protection against respiratory viruses conferred by a prototype live attenuated influenza virus vaccine.

Rathnasinghe, R.·Salvatore, M.·Zheng, H.·Jangra, S.·Kehrer, T.·Mena, I.·Schotsaert, M.·Muster, T.·Palese, P.·Garcia-Sastre, A.
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Abstract

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 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 {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.

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Rathnasinghe, R., Salvatore, M., Zheng, H., Jangra, S., Kehrer, T., Mena, I., Schotsaert, M., Muster, T., Palese, P., Garcia-Sastre, A.. 2021-04-28. Prophylactic protection against respiratory viruses conferred by a prototype live attenuated influenza virus vaccine.. https://doi.org/10.1101/2021.04.28.441797

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