Effects of cellular receptors on the vaccine efficacies of adenovirus vector-based vaccines following intramuscular and intranasal administration

Onishi, Rika; Shiota, Aoi; Nakatani, Hayato; Tachibana, Masashi; Shimizu, Kahori; Hirai, Toshiro; Yoshioka, Yasuo; Sakurai, Fuminori; Mizuguchi, Hiroyuki

doi:https://doi.org/10.1038/s41598-026-49127-5

Effects of cellular receptors on the vaccine efficacies of adenovirus vector-based vaccines following intramuscular and intranasal administration

Onishi, Rika; Shiota, Aoi; Nakatani, Hayato et al.

Scientific Reports, 2026, 16, 19154

Number of Access:778（2026-11-12 09:48 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/106063

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Title	Effects of cellular receptors on the vaccine efficacies of adenovirus vector-based vaccines following intramuscular and intranasal administration
Creator	CreatorName Onishi, Rika
	CreatorName Shiota, Aoi
	CreatorName Nakatani, Hayato
	NRID 1000080513449 1000080513449 CreatorName Tachibana, Masashi
	NRID 1000050737749 1000050737749 ORCID 0000-0003-1574-5526 0000-0003-1574-5526 researchmap permalink kahorishimizu kahorishimizu CreatorName Shimizu, Kahori
	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
	NRID 1000000392308 1000000392308 ORCID 0000-0002-7265-9221 0000-0002-7265-9221 researchmap permalink read0076530 read0076530 Scopus Author ID 55502847200 55502847200 CreatorName Yoshioka, Yasuo
	NRID 1000070370939 1000070370939 CreatorName Sakurai, Fuminori
	NRID 1000050311387 1000050311387 ORCID 0000-0003-0594-8178 0000-0003-0594-8178 researchmap permalink read0165079 read0165079 Scopus Author ID 57195381326 57195381326 CreatorName Mizuguchi, Hiroyuki
Subject	Adenovirus vector vaccine
	Capsid modification
	Cellular receptor
	Coxsackievirus-adenovirus receptor
	Factor X
	αv-integrins
Description	Onishi R., Shiota A., Nakatani H., et al. Effects of cellular receptors on the vaccine efficacies of adenovirus vector-based vaccines following intramuscular and intranasal administration. Scientific Reports 16, 19154 (2026); https://doi.org/10.1038/s41598-026-49127-5.
Abstract	Adenovirus (Ad) vectors are a promising next-generation vaccine modality currently under development. An Ad particle is composed of three major capsid proteins—fiber, penton base, and hexon—that play critical roles in cellular entry. However, the extents to which the receptor-mediated cellular entry pathways influence the efficacy of Ad vector-based vaccines are not well understood. In this study, we examined the effects of the cellular uptake pathway on the vaccine efficacy of Ad vectors by using the β-galactosidase (β-gal)-expressing, capsid-modified Ad vectors that utilize the different cellular entry routes. Following intramuscular vaccination, all capsid-modified Ad vectors induced serum anti-β-gal antibody levels comparable to those induced by the conventional Ad vector. In contrast, after intranasal vaccination, the Ad vectors with mutations in the penton base or hexon elicited anti-β-gal antibody titers in the serum, bronchoalveolar lavage fluid (BALF), and nasal wash at levels comparable with the conventional Ad vector. On the other hand, the coxsackievirus-adenovirus receptor (CAR)-binding-ablated Ad vector exhibited a significant reduction in the anti-β-gal IgG titers in the serum and BALF, and anti-β-gal IgA titers in the BALF and nasal wash. These findings highlight that CAR-mediated transduction is crucial for efficient vaccination with an Ad vector after intranasal administration.
Publisher	Nature Research
Source Title	Scientific Reports
Volume (Issue)	16
Page	19154
Date of Issued	2026-04-25
Language	English
Handle URL	https://hdl.handle.net/11094/106063
eISSN	20452322
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/s41598-026-49127-5
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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	Scientific Reports. 2026, 16, p. 19154
DC.title	Effects of cellular receptors on the vaccine efficacies of adenovirus vector-based vaccines following intramuscular and intranasal administration
DC.creator	Onishi, Rika
	Shiota, Aoi
	Nakatani, Hayato
	Tachibana, Masashi
	Shimizu, Kahori
	Hirai, Toshiro
	Yoshioka, Yasuo
	Sakurai, Fuminori
	Mizuguchi, Hiroyuki
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2026-04-25
DC.identifier	https://doi.org/10.1038/s41598-026-49127-5
DC.subject	Adenovirus vector vaccine
	Capsid modification
	Cellular receptor
	Coxsackievirus-adenovirus receptor
	Factor X
	αv-integrins
DC.description	Onishi R., Shiota A., Nakatani H., et al. Effects of cellular receptors on the vaccine efficacies of adenovirus vector-based vaccines following intramuscular and intranasal administration. Scientific Reports 16, 19154 (2026); https://doi.org/10.1038/s41598-026-49127-5.
DCTERMS.abstract	Adenovirus (Ad) vectors are a promising next-generation vaccine modality currently under development. An Ad particle is composed of three major capsid proteins—fiber, penton base, and hexon—that play critical roles in cellular entry. However, the extents to which the receptor-mediated cellular entry pathways influence the efficacy of Ad vector-based vaccines are not well understood. In this study, we examined the effects of the cellular uptake pathway on the vaccine efficacy of Ad vectors by using the β-galactosidase (β-gal)-expressing, capsid-modified Ad vectors that utilize the different cellular entry routes. Following intramuscular vaccination, all capsid-modified Ad vectors induced serum anti-β-gal antibody levels comparable to those induced by the conventional Ad vector. In contrast, after intranasal vaccination, the Ad vectors with mutations in the penton base or hexon elicited anti-β-gal antibody titers in the serum, bronchoalveolar lavage fluid (BALF), and nasal wash at levels comparable with the conventional Ad vector. On the other hand, the coxsackievirus-adenovirus receptor (CAR)-binding-ablated Ad vector exhibited a significant reduction in the anti-β-gal IgG titers in the serum and BALF, and anti-β-gal IgA titers in the BALF and nasal wash. These findings highlight that CAR-mediated transduction is crucial for efficient vaccination with an Ad vector after intranasal administration.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	106063
citation_title	Effects of cellular receptors on the vaccine efficacies of adenovirus vector-based vaccines following intramuscular and intranasal administration
citation_author	Onishi, Rika
	Shiota, Aoi
	Nakatani, Hayato
	Tachibana, Masashi
	Shimizu, Kahori
	Hirai, Toshiro
	Yoshioka, Yasuo
	Sakurai, Fuminori
	Mizuguchi, Hiroyuki
citation_publisher	Nature Research
citation_language	English
citation_date	2026-04-25
citation_journal_title	Scientific Reports
citation_volume	16
citation_firstpage	19154
citation_doi	https://doi.org/10.1038/s41598-026-49127-5
citation_public_url	https://hdl.handle.net/11094/106063

Effects of cellular receptors on the vaccine efficacies of adenovirus vector-based vaccines following intramuscular and intranasal administration

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