Cargando…

Induction of Mucosal IgA–Mediated Protective Immunity Against Nontypeable Haemophilus influenzae Infection by a Cationic Nanogel–Based P6 Nasal Vaccine

Nontypeable Haemophilus influenzae (NTHi) strains form a major group of pathogenic bacteria that colonizes the nasopharynx and causes otitis media in young children. At present, there is no licensed vaccine for NTHi. Because NTHi colonizes the upper respiratory tract and forms biofilms that cause su...

Descripción completa

Detalles Bibliográficos
Autores principales: Nakahashi-Ouchida, Rika, Mori, Hiromi, Yuki, Yoshikazu, Umemoto, Shingo, Hirano, Takashi, Uchida, Yohei, Machita, Tomonori, Yamanoue, Tomoyuki, Sawada, Shin-ichi, Suzuki, Masashi, Fujihashi, Kohtaro, Akiyoshi, Kazunari, Kurono, Yuichi, Kiyono, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299436/
https://www.ncbi.nlm.nih.gov/pubmed/35874779
http://dx.doi.org/10.3389/fimmu.2022.819859
_version_ 1784750974054694912
author Nakahashi-Ouchida, Rika
Mori, Hiromi
Yuki, Yoshikazu
Umemoto, Shingo
Hirano, Takashi
Uchida, Yohei
Machita, Tomonori
Yamanoue, Tomoyuki
Sawada, Shin-ichi
Suzuki, Masashi
Fujihashi, Kohtaro
Akiyoshi, Kazunari
Kurono, Yuichi
Kiyono, Hiroshi
author_facet Nakahashi-Ouchida, Rika
Mori, Hiromi
Yuki, Yoshikazu
Umemoto, Shingo
Hirano, Takashi
Uchida, Yohei
Machita, Tomonori
Yamanoue, Tomoyuki
Sawada, Shin-ichi
Suzuki, Masashi
Fujihashi, Kohtaro
Akiyoshi, Kazunari
Kurono, Yuichi
Kiyono, Hiroshi
author_sort Nakahashi-Ouchida, Rika
collection PubMed
description Nontypeable Haemophilus influenzae (NTHi) strains form a major group of pathogenic bacteria that colonizes the nasopharynx and causes otitis media in young children. At present, there is no licensed vaccine for NTHi. Because NTHi colonizes the upper respiratory tract and forms biofilms that cause subsequent infectious events, a nasal vaccine that induces NTHi-specific secretory IgA capable of preventing biofilm formation in the respiratory tract is desirable. Here, we developed a cationic cholesteryl pullulan–based (cCHP nanogel) nasal vaccine containing the NTHi surface antigen P6 (cCHP-P6) as a universal vaccine antigen, because P6 expression is conserved among 90% of NTHi strains. Nasal immunization of mice with cCHP-P6 effectively induced P6-specific IgA in mucosal fluids, including nasal and middle ear washes. The vaccine-induced P6-specific IgA showed direct binding to the NTHi via the surface P6 proteins, resulting in the inhibition of NTHi biofilm formation. cCHP-P6 nasal vaccine thus protected mice from intranasal NTHi challenge by reducing NTHi colonization of nasal tissues and eventually eliminated the bacteria. In addition, the vaccine-induced IgA bound to different NTHi clinical isolates from patients with otitis media and inhibited NTHi attachment in a three-dimensional in vitro model of the human nasal epithelial surface. Therefore, the cCHP-P6 nanogel nasal vaccine induced effective protection in the airway mucosa, making it a strong vaccine candidate for preventing NTHi-induced infectious diseases, such as otitis media, sinusitis, and pneumonia.
format Online
Article
Text
id pubmed-9299436
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-92994362022-07-21 Induction of Mucosal IgA–Mediated Protective Immunity Against Nontypeable Haemophilus influenzae Infection by a Cationic Nanogel–Based P6 Nasal Vaccine Nakahashi-Ouchida, Rika Mori, Hiromi Yuki, Yoshikazu Umemoto, Shingo Hirano, Takashi Uchida, Yohei Machita, Tomonori Yamanoue, Tomoyuki Sawada, Shin-ichi Suzuki, Masashi Fujihashi, Kohtaro Akiyoshi, Kazunari Kurono, Yuichi Kiyono, Hiroshi Front Immunol Immunology Nontypeable Haemophilus influenzae (NTHi) strains form a major group of pathogenic bacteria that colonizes the nasopharynx and causes otitis media in young children. At present, there is no licensed vaccine for NTHi. Because NTHi colonizes the upper respiratory tract and forms biofilms that cause subsequent infectious events, a nasal vaccine that induces NTHi-specific secretory IgA capable of preventing biofilm formation in the respiratory tract is desirable. Here, we developed a cationic cholesteryl pullulan–based (cCHP nanogel) nasal vaccine containing the NTHi surface antigen P6 (cCHP-P6) as a universal vaccine antigen, because P6 expression is conserved among 90% of NTHi strains. Nasal immunization of mice with cCHP-P6 effectively induced P6-specific IgA in mucosal fluids, including nasal and middle ear washes. The vaccine-induced P6-specific IgA showed direct binding to the NTHi via the surface P6 proteins, resulting in the inhibition of NTHi biofilm formation. cCHP-P6 nasal vaccine thus protected mice from intranasal NTHi challenge by reducing NTHi colonization of nasal tissues and eventually eliminated the bacteria. In addition, the vaccine-induced IgA bound to different NTHi clinical isolates from patients with otitis media and inhibited NTHi attachment in a three-dimensional in vitro model of the human nasal epithelial surface. Therefore, the cCHP-P6 nanogel nasal vaccine induced effective protection in the airway mucosa, making it a strong vaccine candidate for preventing NTHi-induced infectious diseases, such as otitis media, sinusitis, and pneumonia. Frontiers Media S.A. 2022-07-06 /pmc/articles/PMC9299436/ /pubmed/35874779 http://dx.doi.org/10.3389/fimmu.2022.819859 Text en Copyright © 2022 Nakahashi-Ouchida, Mori, Yuki, Umemoto, Hirano, Uchida, Machita, Yamanoue, Sawada, Suzuki, Fujihashi, Akiyoshi, Kurono and Kiyono https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Nakahashi-Ouchida, Rika
Mori, Hiromi
Yuki, Yoshikazu
Umemoto, Shingo
Hirano, Takashi
Uchida, Yohei
Machita, Tomonori
Yamanoue, Tomoyuki
Sawada, Shin-ichi
Suzuki, Masashi
Fujihashi, Kohtaro
Akiyoshi, Kazunari
Kurono, Yuichi
Kiyono, Hiroshi
Induction of Mucosal IgA–Mediated Protective Immunity Against Nontypeable Haemophilus influenzae Infection by a Cationic Nanogel–Based P6 Nasal Vaccine
title Induction of Mucosal IgA–Mediated Protective Immunity Against Nontypeable Haemophilus influenzae Infection by a Cationic Nanogel–Based P6 Nasal Vaccine
title_full Induction of Mucosal IgA–Mediated Protective Immunity Against Nontypeable Haemophilus influenzae Infection by a Cationic Nanogel–Based P6 Nasal Vaccine
title_fullStr Induction of Mucosal IgA–Mediated Protective Immunity Against Nontypeable Haemophilus influenzae Infection by a Cationic Nanogel–Based P6 Nasal Vaccine
title_full_unstemmed Induction of Mucosal IgA–Mediated Protective Immunity Against Nontypeable Haemophilus influenzae Infection by a Cationic Nanogel–Based P6 Nasal Vaccine
title_short Induction of Mucosal IgA–Mediated Protective Immunity Against Nontypeable Haemophilus influenzae Infection by a Cationic Nanogel–Based P6 Nasal Vaccine
title_sort induction of mucosal iga–mediated protective immunity against nontypeable haemophilus influenzae infection by a cationic nanogel–based p6 nasal vaccine
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299436/
https://www.ncbi.nlm.nih.gov/pubmed/35874779
http://dx.doi.org/10.3389/fimmu.2022.819859
work_keys_str_mv AT nakahashiouchidarika inductionofmucosaligamediatedprotectiveimmunityagainstnontypeablehaemophilusinfluenzaeinfectionbyacationicnanogelbasedp6nasalvaccine
AT morihiromi inductionofmucosaligamediatedprotectiveimmunityagainstnontypeablehaemophilusinfluenzaeinfectionbyacationicnanogelbasedp6nasalvaccine
AT yukiyoshikazu inductionofmucosaligamediatedprotectiveimmunityagainstnontypeablehaemophilusinfluenzaeinfectionbyacationicnanogelbasedp6nasalvaccine
AT umemotoshingo inductionofmucosaligamediatedprotectiveimmunityagainstnontypeablehaemophilusinfluenzaeinfectionbyacationicnanogelbasedp6nasalvaccine
AT hiranotakashi inductionofmucosaligamediatedprotectiveimmunityagainstnontypeablehaemophilusinfluenzaeinfectionbyacationicnanogelbasedp6nasalvaccine
AT uchidayohei inductionofmucosaligamediatedprotectiveimmunityagainstnontypeablehaemophilusinfluenzaeinfectionbyacationicnanogelbasedp6nasalvaccine
AT machitatomonori inductionofmucosaligamediatedprotectiveimmunityagainstnontypeablehaemophilusinfluenzaeinfectionbyacationicnanogelbasedp6nasalvaccine
AT yamanouetomoyuki inductionofmucosaligamediatedprotectiveimmunityagainstnontypeablehaemophilusinfluenzaeinfectionbyacationicnanogelbasedp6nasalvaccine
AT sawadashinichi inductionofmucosaligamediatedprotectiveimmunityagainstnontypeablehaemophilusinfluenzaeinfectionbyacationicnanogelbasedp6nasalvaccine
AT suzukimasashi inductionofmucosaligamediatedprotectiveimmunityagainstnontypeablehaemophilusinfluenzaeinfectionbyacationicnanogelbasedp6nasalvaccine
AT fujihashikohtaro inductionofmucosaligamediatedprotectiveimmunityagainstnontypeablehaemophilusinfluenzaeinfectionbyacationicnanogelbasedp6nasalvaccine
AT akiyoshikazunari inductionofmucosaligamediatedprotectiveimmunityagainstnontypeablehaemophilusinfluenzaeinfectionbyacationicnanogelbasedp6nasalvaccine
AT kuronoyuichi inductionofmucosaligamediatedprotectiveimmunityagainstnontypeablehaemophilusinfluenzaeinfectionbyacationicnanogelbasedp6nasalvaccine
AT kiyonohiroshi inductionofmucosaligamediatedprotectiveimmunityagainstnontypeablehaemophilusinfluenzaeinfectionbyacationicnanogelbasedp6nasalvaccine