Hypertonic intranasal vaccines gain nasal epithelia access to exert strong immunogenicity

Hashimoto, Soichiro; Hirai, Toshiro; Ueda, Koki; Kakihara, Mako; Tokunoh, Nagisa; Ono, Chikako; Matsuura, Yoshiharu; Takayama, Kazuo; Yoshioka, Yasuo

doi:https://doi.org/10.1016/j.mucimm.2025.03.006

Hypertonic intranasal vaccines gain nasal epithelia access to exert strong immunogenicity

Hashimoto, Soichiro; Hirai, Toshiro; Ueda, Koki et al.

Mucosal Immunology, 2025, 18(4), 793-809

Number of Access:21（2025-12-03 09:54 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/102928

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Title	Hypertonic intranasal vaccines gain nasal epithelia access to exert strong immunogenicity
Creator	CreatorName Hashimoto, Soichiro
	NRID 1000000895815 1000000895815 ORCID 0000-0002-9212-1664 0000-0002-9212-1664 researchmap permalink toshiro.hirai toshiro.hirai Scopus Author ID 55628552543 55628552543 CreatorName Hirai, Toshiro
	CreatorName Ueda, Koki
	CreatorName Kakihara, Mako
	CreatorName Tokunoh, Nagisa
	NRID 1000030626437 1000030626437 researchmap permalink ChikakoOno ChikakoOno Scopus Author ID 54990934700 54990934700 CreatorName Ono, Chikako
	NRID 1000050157252 1000050157252 researchmap permalink matsuura_123 matsuura_123 CreatorName Matsuura, Yoshiharu
	NRID 1000010759509 1000010759509 CreatorName Takayama, Kazuo
	NRID 1000000392308 1000000392308 ORCID 0000-0002-7265-9221 0000-0002-7265-9221 researchmap permalink read0076530 read0076530 Scopus Author ID 55502847200 55502847200 CreatorName Yoshioka, Yasuo
Subject	Adenoviral vector
	Hypertonic
	Intranasal vaccine
	Resident memory T cells
	Subunit
Description	Hashimoto S., Hirai T., Ueda K., et al. Hypertonic intranasal vaccines gain nasal epithelia access to exert strong immunogenicity. Mucosal Immunology 18, 793 (2025); https://doi.org/10.1016/j.mucimm.2025.03.006.
Abstract	Intranasal vaccines potentially offer superior protection against viral infections compared with injectable vaccines. The immunogenicity of intranasal vaccines including adenovirus vector (AdV), has room for improvement, while few options are available for safe execution. In this study, we demonstrate that modifying a basic parameter of vaccine formulation, i.e., osmolarity, can significantly enhance the immunogenicity of intranasal vaccines. Addition of glycerol to AdV intranasal vaccine solutions, unlike other viscous additives, enhanced systemic and mucosal antibodies as well as resident memory T cells in the nasal tissues, which could protect nasal tissue and the lungs against influenza virus. While viscous glycerol could not prolong intranasal retention of solutes, it promoted AdV infection of nasal epithelial cells by facilitating AdV access to the nasal epithelial cell. The enhanced immunogenicity was induced by the hypertonicity of vaccine preparations and sodium chloride, glucose, and mannitol demonstrated the capacity to enhance immunogenicity. Moreover, hypertonic glycerol enhanced the immunogenicity of adjuvanted subunit intranasal vaccines, but not subunit vaccines without adjuvant or injectable vaccines. Overall, the delivery of intranasal vaccines to nasal epithelial cells could be improved through a simple approach, potentially resulting in stronger immunogenicity for certain vaccines.
Publisher	Elsevier B.V.
Source Title	Mucosal Immunology
Volume (Issue)	18(4)
Page	793-809
Date of Issued	2025-08-05
Language	English
Handle URL	https://hdl.handle.net/11094/102928
PISSN	19330219
eISSN	19353456
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1016/j.mucimm.2025.03.006
Access Rights	open access
CopyRight	© 2025. This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. https://creativecommons.org/licenses/by-nc-nd/4.0/
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Mucosal Immunology. 2025, 18(4), p. 793-809
DC.title	Hypertonic intranasal vaccines gain nasal epithelia access to exert strong immunogenicity
DC.creator	Hashimoto, Soichiro
	Hirai, Toshiro
	Ueda, Koki
	Kakihara, Mako
	Tokunoh, Nagisa
	Ono, Chikako
	Matsuura, Yoshiharu
	Takayama, Kazuo
	Yoshioka, Yasuo
DC.publisher	Elsevier B.V.
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-08-05
DC.identifier	https://doi.org/10.1016/j.mucimm.2025.03.006
DC.subject	Adenoviral vector
	Hypertonic
	Intranasal vaccine
	Resident memory T cells
	Subunit
DC.description	Hashimoto S., Hirai T., Ueda K., et al. Hypertonic intranasal vaccines gain nasal epithelia access to exert strong immunogenicity. Mucosal Immunology 18, 793 (2025); https://doi.org/10.1016/j.mucimm.2025.03.006.
DCTERMS.abstract	Intranasal vaccines potentially offer superior protection against viral infections compared with injectable vaccines. The immunogenicity of intranasal vaccines including adenovirus vector (AdV), has room for improvement, while few options are available for safe execution. In this study, we demonstrate that modifying a basic parameter of vaccine formulation, i.e., osmolarity, can significantly enhance the immunogenicity of intranasal vaccines. Addition of glycerol to AdV intranasal vaccine solutions, unlike other viscous additives, enhanced systemic and mucosal antibodies as well as resident memory T cells in the nasal tissues, which could protect nasal tissue and the lungs against influenza virus. While viscous glycerol could not prolong intranasal retention of solutes, it promoted AdV infection of nasal epithelial cells by facilitating AdV access to the nasal epithelial cell. The enhanced immunogenicity was induced by the hypertonicity of vaccine preparations and sodium chloride, glucose, and mannitol demonstrated the capacity to enhance immunogenicity. Moreover, hypertonic glycerol enhanced the immunogenicity of adjuvanted subunit intranasal vaccines, but not subunit vaccines without adjuvant or injectable vaccines. Overall, the delivery of intranasal vaccines to nasal epithelial cells could be improved through a simple approach, potentially resulting in stronger immunogenicity for certain vaccines.
DC.rights	© 2025. This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. https://creativecommons.org/licenses/by-nc-nd/4.0/
DC.format	102928
citation_title	Hypertonic intranasal vaccines gain nasal epithelia access to exert strong immunogenicity
citation_author	Hashimoto, Soichiro
	Hirai, Toshiro
	Ueda, Koki
	Kakihara, Mako
	Tokunoh, Nagisa
	Ono, Chikako
	Matsuura, Yoshiharu
	Takayama, Kazuo
	Yoshioka, Yasuo
citation_publisher	Elsevier B.V.
citation_language	English
citation_date	2025-08-05
citation_journal_title	Mucosal Immunology
citation_volume	18
citation_issue	4
citation_firstpage	793
citation_lastpage	809
citation_doi	https://doi.org/10.1016/j.mucimm.2025.03.006
citation_public_url	https://hdl.handle.net/11094/102928

Hypertonic intranasal vaccines gain nasal epithelia access to exert strong immunogenicity

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