Impaired airway mucociliary function reduces antigen-specific IgA immune response to immunization with a claudin-4-targeting nasal vaccine in mice

• Suzuki, Hidehiko

  Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Ibaraki･Laboratory of Bio-Functional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University

• Nagatake, Takahiro

  Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Ibaraki

• Nasu, Ayaka

  Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Ibaraki

• Lan, Huangwenxian

  Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Ibaraki

• Ikegami, Koji

  International Mass Imaging Center and Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine

• Setou, Mitsutoshi

  International Mass Imaging Center and Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine･Preeminent Medical Photonics Education & Research Center, Shizuoka･Department of Anatomy, The university of Hong Kong

• Hamazaki, Yoko

  Center for iPS Cell Research and Application (CiRA), Laboratory of Immunobiology, Graduate school of Medicine, Kyoto University

• Kiyono, Hiroshi

  Division of Mucosal Immunology, Department of Microbiology and Immunology and International Research and Development Center for Mucosal Vaccines, The Institute of Medical Sciences, The University of Tokyo･Department of Immunology, Graduate School of Medicine, Chiba University

• Yagi, Kiyohito

  Laboratory of Bio-Functional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University

• Kondoh, Masuo

  Graduate School of Pharmaceutical Sciences, Osaka University

• Kunisawa, Jun

  Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Ibaraki･Division of Mucosal Immunology, Department of Microbiology and Immunology and International Research and Development Center for Mucosal Vaccines, The Institute of Medical Sciences, The University of Tokyo･Department of Microbiology and Infectious Diseases, Kobe University Graduate School of Medicine･Graduate School of Medicine, Graduate School of Pharmaceutical Sciences, and Graduate School of Dentistry, Osaka University

Abstract

Vaccine delivery is an essential element for the development of mucosal vaccine, but it remains to be investigated how physical barriers such as mucus and cilia affect vaccine delivery efficacy. Previously, we reported that C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) targeted claudin-4, which is expressed by the epithelium associated with nasopharynx-associated lymphoid tissue (NALT), and could be effective as a nasal vaccine delivery. Mice lacking tubulin tyrosine ligase-like family, member 1 (Ttll1-KO mice) showed mucus accumulation in nasal cavity due to the impaired motility of respiratory cilia. Ttll1-KO mice nasally immunized with C-CPE fused to pneumococcal surface protein A (PspA-C-CPE) showed reduced PspA-specific nasal IgA responses, impaired germinal center formation, and decreased germinal center B-cells and follicular helper T cells in the NALT. Although there was no change in the expression of claudin-4 in the NALT epithelium in Ttll1-KO mice, the epithelium was covered by a dense mucus that prevented the binding of PspA-C-CPE to NALT. However, administration of expectorant N-acetylcysteine removed the mucus and rescued the PspA-specific nasal IgA response. These results show that the accumulation of mucus caused by impaired respiratory cilia function is an interfering factor in the C-CPE-based claudin-4-targeting nasal vaccine.

Journal

• Scientific Reports

  Scientific Reports 8 2904-, 2018-02-13

  Springer Nature

Keywords

• Multidisciplinary

Details

• CRID: 1050001338209199872
• NII Article ID: 120006551757
• ISSN: 20452322
• DOI: 10.1038/s41598-018-21120-7
• HANDLE: 2433/236110
• Web Site: https://www.nature.com/articles/s41598-018-21120-7
• Web Site: https://www.nature.com/articles/s41598-018-21120-7.pdf
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
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  • CiNii Articles
  • KAKEN