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Disruption of nasal bacteria enhances protective immune responses to influenza A virus and SARS-CoV-2 infection in mice

Minami Nagai, View ORCID ProfileMiyu Moriyama, View ORCID ProfileTakeshi Ichinohe
doi: https://doi.org/10.1101/2020.12.25.424300
Minami Nagai
1Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
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Miyu Moriyama
1Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
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Takeshi Ichinohe
1Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
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  • ORCID record for Takeshi Ichinohe
  • For correspondence: ichinohe@ims.u-tokyo.ac.jp
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Abstract

Gut microbiota plays a critical role in the induction of adaptive immune responses to influenza virus infection. However, the role of nasal bacteria in the induction of the virus-specific adaptive immunity is less clear. Here we demonstrate that while intranasal administration of influenza virus hemagglutinin vaccine alone was insufficient to induce the vaccine-specific antibody responses, disruption of nasal bacteria by lysozyme or addition of culturable oral bacteria from a healthy human volunteer rescued inability of the nasal bacteria to generate antibody responses to intranasally administered the split-virus vaccine. Myd88-depdnent signaling in the hematopoietic compartment was required for adjuvant activity of intranasally administered oral bacteria. In addition, we found that the oral bacteria-combined intranasal vaccine induced protective antibody response to influenza virus and SARS-CoV-2 infection. Our findings here have identified a previously unappreciated role for nasal bacteria in the induction of the virus-specific adaptive immune responses.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted December 27, 2020.
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Disruption of nasal bacteria enhances protective immune responses to influenza A virus and SARS-CoV-2 infection in mice
Minami Nagai, Miyu Moriyama, Takeshi Ichinohe
bioRxiv 2020.12.25.424300; doi: https://doi.org/10.1101/2020.12.25.424300
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Disruption of nasal bacteria enhances protective immune responses to influenza A virus and SARS-CoV-2 infection in mice
Minami Nagai, Miyu Moriyama, Takeshi Ichinohe
bioRxiv 2020.12.25.424300; doi: https://doi.org/10.1101/2020.12.25.424300

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