Tags

Type your tag names separated by a space and hit enter

Oral Bacteria Combined with an Intranasal Vaccine Protect from Influenza A Virus and SARS-CoV-2 Infection.
mBio. 2021 08 31; 12(4):e0159821.MBIO

Abstract

The 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 found that disruption of nasal bacteria by intranasal application of antibiotics before influenza virus infection enhanced the virus-specific antibody response in a MyD88-dependent manner. Similarly, disruption of nasal bacteria by lysozyme enhanced antibody responses to intranasally administered influenza virus hemagglutinin (HA) vaccine in a MyD88-dependent manner, suggesting that intranasal application of antibiotics or lysozyme could release bacterial pathogen-associated molecular patterns (PAMPs) from disrupted nasal bacteria that act as mucosal adjuvants by activating the MyD88 signaling pathway. Since commensal bacteria in the nasal mucosal surface were significantly lower than those in the oral cavity, intranasal administration of HA vaccine alone was insufficient to induce the vaccine-specific antibody response. However, intranasal supplementation of cultured oral bacteria from a healthy human volunteer enhanced antibody responses to an intranasally administered HA vaccine. Finally, we demonstrated that oral bacteria combined with an intranasal vaccine protect from influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our results reveal the role of nasal bacteria in the induction of the virus-specific adaptive immunity and provide clues for developing better intranasal vaccines. IMPORTANCE Intranasal vaccination induces the nasal IgA antibody which is protective against respiratory viruses, such as influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, understanding how mucosal immune responses are elicited following viral infection is important for developing better vaccines. Here, we focused on the role of nasal commensal bacteria in the induction of immune responses following influenza virus infection. To deplete nasal bacteria, we intranasally administered antibiotics to mice before influenza virus infection and found that antibiotic-induced disruption of nasal bacteria could release bacterial components which stimulate the virus-specific antibody responses. Since commensal bacteria in nasal mucosa were significantly lower than those in the oral cavity, intranasal administration of split virus vaccine alone was insufficient to induce the vaccine-specific antibody response. However, intranasal supplementation of cultured oral bacteria from a healthy human volunteer enhanced antibody responses to the intranasally administered vaccine. Therefore, both integrity and amounts of nasal bacteria may be critical for an effective intranasal vaccine.

Links

PMC Free PDF

Authors+Show Affiliations

Nagai M
Division 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, Japan.
Moriyama M
Division 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, Japan.
Ichinohe T
Division 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, Japan.

MeSH

Adaptive ImmunityAdjuvants, ImmunologicAdministration, IntranasalAnimalsAntibodies, ViralBacteriaCOVID-19COVID-19 VaccinesCell LineChlorocebus aethiopsDogsHemagglutinin Glycoproteins, Influenza VirusImmunity, MucosalInfluenza A Virus, H1N1 SubtypeInfluenza VaccinesMadin Darby Canine Kidney CellsMiceMice, Inbred BALB CMyeloid Differentiation Factor 88Nasal MucosaOrthomyxoviridae InfectionsPathogen-Associated Molecular Pattern MoleculesSARS-CoV-2VaccinationVero Cells

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34399617

Citation

Nagai, Minami, et al. "Oral Bacteria Combined With an Intranasal Vaccine Protect From Influenza a Virus and SARS-CoV-2 Infection." MBio, vol. 12, no. 4, 2021, pp. e0159821.
Nagai M, Moriyama M, Ichinohe T. Oral Bacteria Combined with an Intranasal Vaccine Protect from Influenza A Virus and SARS-CoV-2 Infection. mBio. 2021;12(4):e0159821.
Nagai, M., Moriyama, M., & Ichinohe, T. (2021). Oral Bacteria Combined with an Intranasal Vaccine Protect from Influenza A Virus and SARS-CoV-2 Infection. MBio, 12(4), e0159821. https://doi.org/10.1128/mBio.01598-21
Nagai M, Moriyama M, Ichinohe T. Oral Bacteria Combined With an Intranasal Vaccine Protect From Influenza a Virus and SARS-CoV-2 Infection. mBio. 2021 08 31;12(4):e0159821. PubMed PMID: 34399617.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oral Bacteria Combined with an Intranasal Vaccine Protect from Influenza A Virus and SARS-CoV-2 Infection. AU - Nagai,Minami, AU - Moriyama,Miyu, AU - Ichinohe,Takeshi, Y1 - 2021/08/17/ PY - 2021/8/18/pubmed PY - 2021/9/15/medline PY - 2021/8/17/entrez KW - SARS-CoV-2 KW - adjuvant KW - intranasal vaccine KW - mucosal immunity SP - e0159821 EP - e0159821 JF - mBio JO - mBio VL - 12 IS - 4 N2 - The 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 found that disruption of nasal bacteria by intranasal application of antibiotics before influenza virus infection enhanced the virus-specific antibody response in a MyD88-dependent manner. Similarly, disruption of nasal bacteria by lysozyme enhanced antibody responses to intranasally administered influenza virus hemagglutinin (HA) vaccine in a MyD88-dependent manner, suggesting that intranasal application of antibiotics or lysozyme could release bacterial pathogen-associated molecular patterns (PAMPs) from disrupted nasal bacteria that act as mucosal adjuvants by activating the MyD88 signaling pathway. Since commensal bacteria in the nasal mucosal surface were significantly lower than those in the oral cavity, intranasal administration of HA vaccine alone was insufficient to induce the vaccine-specific antibody response. However, intranasal supplementation of cultured oral bacteria from a healthy human volunteer enhanced antibody responses to an intranasally administered HA vaccine. Finally, we demonstrated that oral bacteria combined with an intranasal vaccine protect from influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our results reveal the role of nasal bacteria in the induction of the virus-specific adaptive immunity and provide clues for developing better intranasal vaccines. IMPORTANCE Intranasal vaccination induces the nasal IgA antibody which is protective against respiratory viruses, such as influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, understanding how mucosal immune responses are elicited following viral infection is important for developing better vaccines. Here, we focused on the role of nasal commensal bacteria in the induction of immune responses following influenza virus infection. To deplete nasal bacteria, we intranasally administered antibiotics to mice before influenza virus infection and found that antibiotic-induced disruption of nasal bacteria could release bacterial components which stimulate the virus-specific antibody responses. Since commensal bacteria in nasal mucosa were significantly lower than those in the oral cavity, intranasal administration of split virus vaccine alone was insufficient to induce the vaccine-specific antibody response. However, intranasal supplementation of cultured oral bacteria from a healthy human volunteer enhanced antibody responses to the intranasally administered vaccine. Therefore, both integrity and amounts of nasal bacteria may be critical for an effective intranasal vaccine. SN - 2150-7511 UR - https://www.unboundmedicine.com/medline/citation/34399617/Oral_Bacteria_Combined_with_an_Intranasal_Vaccine_Protect_from_Influenza_A_Virus_and_SARS_CoV_2_Infection_ DB - PRIME DP - Unbound Medicine ER -
Grapherence [↓3 ↑45]

Related Citations

More