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Article

Intranasal Immunization with the Influenza A Virus Encoding Truncated NS1 Protein Protects Mice from Heterologous Challenge by Restraining the Inflammatory Response in the Lungs

Smorodintsev Research Institute of Influenza, 197022 St. Petersburg, Russia
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Author to whom correspondence should be addressed.
Academic Editor: Maria G. Isaguliants
Microorganisms 2021, 9(4), 690; https://doi.org/10.3390/microorganisms9040690
Received: 24 February 2021 / Revised: 19 March 2021 / Accepted: 23 March 2021 / Published: 26 March 2021
(This article belongs to the Special Issue Viral Immunogens and Vaccines)
Influenza viruses with an impaired NS1 protein are unable to antagonize the innate immune system and, therefore, are highly immunogenic because of the self-adjuvating effect. Hence, NS1-mutated viruses are considered promising candidates for the development of live-attenuated influenza vaccines and viral vectors for intranasal administration. We investigated whether the immunogenic advantage of the virus expressing only the N-terminal half of the NS1 protein (124 a.a.) can be translated into the induction of protective immunity against a heterologous influenza virus in mice. We found that immunization with either the wild-type A/PR/8/34 (H1N1) influenza strain (A/PR8/NSfull) or its NS1-shortened counterpart (A/PR8/NS124) did not prevent the viral replication in the lungs after the challenge with the A/Aichi/2/68 (H3N2) virus. However, mice immunized with the NS1-shortened virus were better protected from lethality after the challenge with the heterologous virus. Besides showing the enhanced influenza-specific CD8+ T-cellular response in the lungs, immunization with the A/PR8/NS124 virus resulted in reduced concentrations of proinflammatory cytokines and the lower extent of leukocyte infiltration in the lungs after the challenge compared to A/PR8/NSfull or the control group. The data show that intranasal immunization with the NS1-truncated virus may better induce not only effector T-cells but also certain immunoregulatory mechanisms, reducing the severity of the innate immune response after the heterologous challenge. View Full-Text
Keywords: influenza virus; NS1 protein; immune response; immunogenicity; flow cytometry influenza virus; NS1 protein; immune response; immunogenicity; flow cytometry
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MDPI and ACS Style

Vasilyev, K.; Shurygina, A.-P.; Sergeeva, M.; Stukova, M.; Egorov, A. Intranasal Immunization with the Influenza A Virus Encoding Truncated NS1 Protein Protects Mice from Heterologous Challenge by Restraining the Inflammatory Response in the Lungs. Microorganisms 2021, 9, 690. https://doi.org/10.3390/microorganisms9040690

AMA Style

Vasilyev K, Shurygina A-P, Sergeeva M, Stukova M, Egorov A. Intranasal Immunization with the Influenza A Virus Encoding Truncated NS1 Protein Protects Mice from Heterologous Challenge by Restraining the Inflammatory Response in the Lungs. Microorganisms. 2021; 9(4):690. https://doi.org/10.3390/microorganisms9040690

Chicago/Turabian Style

Vasilyev, Kirill, Anna-Polina Shurygina, Maria Sergeeva, Marina Stukova, and Andrej Egorov. 2021. "Intranasal Immunization with the Influenza A Virus Encoding Truncated NS1 Protein Protects Mice from Heterologous Challenge by Restraining the Inflammatory Response in the Lungs" Microorganisms 9, no. 4: 690. https://doi.org/10.3390/microorganisms9040690

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