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.
【저자키워드】 SARS-CoV-2, intranasal vaccine, mucosal immunity, adjuvant, 【초록키워드】 Vaccine, coronavirus, adaptive, Immunity, Vaccines, Influenza, Antibody Response, Infection, Antibiotics, nasal, Influenza virus, severe acute respiratory syndrome Coronavirus, immune responses, Bacteria, gut microbiota, signaling pathway, virus infection, Adaptive immune response, Critical, intranasal, Bacterial, mucosal, administration, PAMPs, adaptive immune responses, Disruption, oral cavity, acute respiratory syndrome, pathogen-associated molecular pattern, commensal bacteria, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, bacterial pathogen, lysozyme, MYD88, significantly lower, Administered, mucosal surface, PROTECT, healthy, intranasally, less, demonstrated, induce, activating, 【제목키워드】 oral, Combined,