Intranasal immunization with an RBD-hemagglutinin fusion protein harnesses preexisting immunity to enhance antigen-specific responses

Kawai, Atsushi; Tokunoh, Nagisa; Kawahara, Eigo; Tamiya, Shigeyuki; Okamura, Shinya; Ono, Chikako; Anindita, Jessica; Tanaka, Hiroki; Akita, Hidetaka; Yamasaki, Sho; Kunisawa, Jun; Okamoto, Toru; Matsuura, Yoshiharu; Hirai, Toshiro; Yoshioka, Yasuo

doi:https://doi.org/10.1172/JCI166827

Intranasal immunization with an RBD-hemagglutinin fusion protein harnesses preexisting immunity to enhance antigen-specific responses

Kawai, Atsushi; Tokunoh, Nagisa; Kawahara, Eigo et al.

Journal of Clinical Investigation, 2023, 133(23), e166827

アクセス数:2,062件（2025-10-24 09:09 集計）

固定URL: https://hdl.handle.net/11094/95675

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タイトル	Intranasal immunization with an RBD-hemagglutinin fusion protein harnesses preexisting immunity to enhance antigen-specific responses
著者	著者名 Kawai, Atsushi
	著者名 Tokunoh, Nagisa
	著者名 Kawahara, Eigo
	NRID 1000090908203 1000090908203 researchmap permalink shigeyuki.tamiya shigeyuki.tamiya 著者名 Tamiya, Shigeyuki
	著者名 Okamura, Shinya
	NRID 1000030626437 1000030626437 researchmap permalink ChikakoOno ChikakoOno Scopus Author ID 54990934700 54990934700 著者名 Ono, Chikako
	著者名 Anindita, Jessica
	著者名 Tanaka, Hiroki
	NRID 1000080344472 1000080344472 著者名 Akita, Hidetaka
	NRID 1000040312946 1000040312946 researchmap permalink read0117961 read0117961 Scopus Author ID 57219186899 57219186899 ORCID 0000-0002-5184-6917 0000-0002-5184-6917 著者名 Yamasaki, Sho
	NRID 1000080376615 1000080376615 researchmap permalink -9871 -9871 著者名 Kunisawa, Jun
	NRID 1000080628595 1000080628595 researchmap permalink TOKAMOTO TOKAMOTO Scopus Author ID 10144905800 10144905800 著者名 Okamoto, Toru
	NRID 1000050157252 1000050157252 researchmap permalink matsuura_123 matsuura_123 著者名 Matsuura, Yoshiharu
	NRID 1000000895815 1000000895815 ORCID 0000-0002-9212-1664 0000-0002-9212-1664 researchmap permalink toshiro.hirai toshiro.hirai Scopus Author ID 55628552543 55628552543 著者名 Hirai, Toshiro
	NRID 1000000392308 1000000392308 researchmap permalink read0076530 read0076530 Scopus Author ID 55502847200 55502847200 ORCID 0000-0002-7265-9221 0000-0002-7265-9221 著者名 Yoshioka, Yasuo
内容	Kawai A., Tokunoh N., Kawahara E., et al. Intranasal immunization with an RBD-hemagglutinin fusion protein harnesses preexisting immunity to enhance antigen-specific responses. Journal of Clinical Investigation 133, e166827 (2023); https://doi.org/10.1172/JCI166827.
抄録	Intranasal vaccines are anticipated to be powerful tools for combating many infectious diseases, including SARS-CoV-2, because they induce not only systemic immunity but also mucosal immunity at the site of initial infection. However, they are generally inefficient in inducing an antigen-specific immune response without adjuvants. Here, we developed an adjuvant-free intranasal vaccine platform that utilizes the preexisting immunity induced by previous infection or vaccination to enhance vaccine effectiveness. We made RBD-HA, a fusion of the receptor-binding domain (RBD) of spike derived from SARS-CoV-2 as a vaccine target with HA derived from influenza A virus (IAV) as a carrier protein. Intranasal immunization of previously IAV-infected mice with RBD-HA without an adjuvant elicited robust production of RBD-specific systemic IgG and mucosal IgA by utilizing both HA-specific preexisting IgG and CD4+ T cells. Consequently, the mice were efficiently protected from SARS-CoV-2 infection. Additionally, we demonstrated the high versatility of this intranasal vaccine platform by assessing various vaccine antigens and preexisting immunity associated with a variety of infectious diseases. The results of this study suggest the promising potential of this intranasal vaccine platform to address problems associated with intranasal vaccines.
出版者	American Society for Clinical Investigation
収録物名	Journal of Clinical Investigation
巻(号)	133(23)
ページ	e166827
刊行年月	2023-12-10
言語	英語
ハンドルURL	https://hdl.handle.net/11094/95675
PISSN	00219738
eISSN	15588238
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1172/JCI166827
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Journal of Clinical Investigation. 2023, 133(23), p. e166827
DC.title	Intranasal immunization with an RBD-hemagglutinin fusion protein harnesses preexisting immunity to enhance antigen-specific responses
DC.creator	Kawai, Atsushi
	Tokunoh, Nagisa
	Kawahara, Eigo
	Tamiya, Shigeyuki
	Okamura, Shinya
	Ono, Chikako
	Anindita, Jessica
	Tanaka, Hiroki
	Akita, Hidetaka
	Yamasaki, Sho
	Kunisawa, Jun
	Okamoto, Toru
	Matsuura, Yoshiharu
	Hirai, Toshiro
	Yoshioka, Yasuo
DC.publisher	American Society for Clinical Investigation
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2023-12-10
DC.identifier	https://doi.org/10.1172/JCI166827
DC.description	Kawai A., Tokunoh N., Kawahara E., et al. Intranasal immunization with an RBD-hemagglutinin fusion protein harnesses preexisting immunity to enhance antigen-specific responses. Journal of Clinical Investigation 133, e166827 (2023); https://doi.org/10.1172/JCI166827.
DCTERMS.abstract	Intranasal vaccines are anticipated to be powerful tools for combating many infectious diseases, including SARS-CoV-2, because they induce not only systemic immunity but also mucosal immunity at the site of initial infection. However, they are generally inefficient in inducing an antigen-specific immune response without adjuvants. Here, we developed an adjuvant-free intranasal vaccine platform that utilizes the preexisting immunity induced by previous infection or vaccination to enhance vaccine effectiveness. We made RBD-HA, a fusion of the receptor-binding domain (RBD) of spike derived from SARS-CoV-2 as a vaccine target with HA derived from influenza A virus (IAV) as a carrier protein. Intranasal immunization of previously IAV-infected mice with RBD-HA without an adjuvant elicited robust production of RBD-specific systemic IgG and mucosal IgA by utilizing both HA-specific preexisting IgG and CD4+ T cells. Consequently, the mice were efficiently protected from SARS-CoV-2 infection. Additionally, we demonstrated the high versatility of this intranasal vaccine platform by assessing various vaccine antigens and preexisting immunity associated with a variety of infectious diseases. The results of this study suggest the promising potential of this intranasal vaccine platform to address problems associated with intranasal vaccines.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	95675
citation_title	Intranasal immunization with an RBD-hemagglutinin fusion protein harnesses preexisting immunity to enhance antigen-specific responses
citation_author	Kawai, Atsushi
	Tokunoh, Nagisa
	Kawahara, Eigo
	Tamiya, Shigeyuki
	Okamura, Shinya
	Ono, Chikako
	Anindita, Jessica
	Tanaka, Hiroki
	Akita, Hidetaka
	Yamasaki, Sho
	Kunisawa, Jun
	Okamoto, Toru
	Matsuura, Yoshiharu
	Hirai, Toshiro
	Yoshioka, Yasuo
citation_publisher	American Society for Clinical Investigation
citation_language	英語
citation_date	2023-12-10
citation_journal_title	Journal of Clinical Investigation
citation_volume	133
citation_issue	23
citation_firstpage	e166827
citation_doi	https://doi.org/10.1172/JCI166827
citation_public_url	https://hdl.handle.net/11094/95675

Intranasal immunization with an RBD-hemagglutinin fusion protein harnesses preexisting immunity to enhance antigen-specific responses

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