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

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...

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Autores principales: Suzuki, Hidehiko, Nagatake, Takahiro, Nasu, Ayaka, Lan, Huangwenxian, Ikegami, Koji, Setou, Mitsutoshi, Hamazaki, Yoko, Kiyono, Hiroshi, Yagi, Kiyohito, Kondoh, Masuo, Kunisawa, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811541/
https://www.ncbi.nlm.nih.gov/pubmed/29440671
http://dx.doi.org/10.1038/s41598-018-21120-7
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author Suzuki, Hidehiko
Nagatake, Takahiro
Nasu, Ayaka
Lan, Huangwenxian
Ikegami, Koji
Setou, Mitsutoshi
Hamazaki, Yoko
Kiyono, Hiroshi
Yagi, Kiyohito
Kondoh, Masuo
Kunisawa, Jun
author_facet Suzuki, Hidehiko
Nagatake, Takahiro
Nasu, Ayaka
Lan, Huangwenxian
Ikegami, Koji
Setou, Mitsutoshi
Hamazaki, Yoko
Kiyono, Hiroshi
Yagi, Kiyohito
Kondoh, Masuo
Kunisawa, Jun
author_sort Suzuki, Hidehiko
collection PubMed
description 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.
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spelling pubmed-58115412018-02-16 Impaired airway mucociliary function reduces antigen-specific IgA immune response to immunization with a claudin-4-targeting nasal vaccine in mice Suzuki, Hidehiko Nagatake, Takahiro Nasu, Ayaka Lan, Huangwenxian Ikegami, Koji Setou, Mitsutoshi Hamazaki, Yoko Kiyono, Hiroshi Yagi, Kiyohito Kondoh, Masuo Kunisawa, Jun Sci Rep Article 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. Nature Publishing Group UK 2018-02-13 /pmc/articles/PMC5811541/ /pubmed/29440671 http://dx.doi.org/10.1038/s41598-018-21120-7 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Suzuki, Hidehiko
Nagatake, Takahiro
Nasu, Ayaka
Lan, Huangwenxian
Ikegami, Koji
Setou, Mitsutoshi
Hamazaki, Yoko
Kiyono, Hiroshi
Yagi, Kiyohito
Kondoh, Masuo
Kunisawa, Jun
Impaired airway mucociliary function reduces antigen-specific IgA immune response to immunization with a claudin-4-targeting nasal vaccine in mice
title Impaired airway mucociliary function reduces antigen-specific IgA immune response to immunization with a claudin-4-targeting nasal vaccine in mice
title_full Impaired airway mucociliary function reduces antigen-specific IgA immune response to immunization with a claudin-4-targeting nasal vaccine in mice
title_fullStr Impaired airway mucociliary function reduces antigen-specific IgA immune response to immunization with a claudin-4-targeting nasal vaccine in mice
title_full_unstemmed Impaired airway mucociliary function reduces antigen-specific IgA immune response to immunization with a claudin-4-targeting nasal vaccine in mice
title_short Impaired airway mucociliary function reduces antigen-specific IgA immune response to immunization with a claudin-4-targeting nasal vaccine in mice
title_sort impaired airway mucociliary function reduces antigen-specific iga immune response to immunization with a claudin-4-targeting nasal vaccine in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811541/
https://www.ncbi.nlm.nih.gov/pubmed/29440671
http://dx.doi.org/10.1038/s41598-018-21120-7
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