Recombinant RSV G protein vaccine induces enhanced respiratory disease via IL-13 and mucin overproduction

Kawahara, Eigo; Senpuku, Kota; Kawaguchi, Yoshino; Yamamoto, Shinya; Yasuda, Koubun; Kuroda, Etsushi; Ouji-Sageshima, Noriko; Ito, Toshihiro; Hirai, Toshiro; Shibata, Takehiko; Yoshioka, Yasuo

doi:https://doi.org/10.1038/S41541-024-00987-W

Recombinant RSV G protein vaccine induces enhanced respiratory disease via IL-13 and mucin overproduction

Kawahara, Eigo; Senpuku, Kota; Kawaguchi, Yoshino et al.

npj Vaccines, 2024, 9, 187

Number of Access:900（2025-08-14 02:19 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/98546

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Title	Recombinant RSV G protein vaccine induces enhanced respiratory disease via IL-13 and mucin overproduction
Creator	NRID 1000091004498 1000091004498 CreatorName Kawahara, Eigo
	CreatorName Senpuku, Kota
	CreatorName Kawaguchi, Yoshino
	CreatorName Yamamoto, Shinya
	NRID 1000050333539 1000050333539 CreatorName Yasuda, Koubun
	NRID 1000010299604 1000010299604 CreatorName Kuroda, Etsushi
	NRID 1000030398432 1000030398432 CreatorName Ouji-Sageshima, Noriko
	NRID 1000000595712 1000000595712 CreatorName Ito, Toshihiro
	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 1000000739196 1000000739196 CreatorName Shibata, Takehiko
	NRID 1000000392308 1000000392308 researchmap permalink read0076530 read0076530 Scopus Author ID 55502847200 55502847200 ORCID 0000-0002-7265-9221 0000-0002-7265-9221 CreatorName Yoshioka, Yasuo
Description	Kawahara E., Senpuku K., Kawaguchi Y., et al. Recombinant RSV G protein vaccine induces enhanced respiratory disease via IL-13 and mucin overproduction. npj Vaccines 9, 187 (2024); https://doi.org/10.1038/S41541-024-00987-W.
Abstract	The G protein expressed on the surface of respiratory syncytial virus (RSV) is important for adhesion to host cells and as a vaccine target antigen. The corresponding vaccines can effectively eliminate RSV. However, they exacerbate pulmonary immunopathology including eosinophilic infiltration in the lungs after an RSV challenge in animal models, raising concerns about enhanced respiratory disease (ERD); thus, approaches that mitigate these effects are urgently needed. Herein, we aimed to examine the mechanisms of G protein vaccine-induced ERD in mice, using recombinant G protein as a vaccine antigen. After the RSV challenge, G protein-vaccinated mice exhibited lung weight gain, lung tissue damage, and increased infiltration of eosinophils, neutrophils, and CD4+ T cells into the lungs. We set lung weight gain as the endpoint for ERD and examined the impact of each infiltrating cell on lung weight gain. We observed that CD4+ T cells, but not eosinophils or neutrophils, that infiltrate the lungs are responsible for lung weight gain. In addition, T helper 2 cell-mediated IL-13 induced mucin hypersecretion and lung weight gain. Mucin hypersecretion may contribute to weight gain in the lungs. In conclusion, our results indicate a novel mechanism of G protein vaccine-induced ERD via IL-13 and mucin hypersecretion, which could lead to the development of safe G protein vaccines and the elucidation of the causes of ERD associated with other vaccines.
Publisher	Nature Research
Source Title	npj Vaccines
Volume (Issue)	9
Page	187
Date of Issued	2024-10-12
Language	English
Handle URL	https://hdl.handle.net/11094/98546
eISSN	20590105
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/S41541-024-00987-W
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 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
DCTERMS.bibliographicCitation	npj Vaccines. 2024, 9, p. 187
DC.title	Recombinant RSV G protein vaccine induces enhanced respiratory disease via IL-13 and mucin overproduction
DC.creator	Kawahara, Eigo
	Senpuku, Kota
	Kawaguchi, Yoshino
	Yamamoto, Shinya
	Yasuda, Koubun
	Kuroda, Etsushi
	Ouji-Sageshima, Noriko
	Ito, Toshihiro
	Hirai, Toshiro
	Shibata, Takehiko
	Yoshioka, Yasuo
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-10-12
DC.identifier	https://doi.org/10.1038/S41541-024-00987-W
DC.description	Kawahara E., Senpuku K., Kawaguchi Y., et al. Recombinant RSV G protein vaccine induces enhanced respiratory disease via IL-13 and mucin overproduction. npj Vaccines 9, 187 (2024); https://doi.org/10.1038/S41541-024-00987-W.
DCTERMS.abstract	The G protein expressed on the surface of respiratory syncytial virus (RSV) is important for adhesion to host cells and as a vaccine target antigen. The corresponding vaccines can effectively eliminate RSV. However, they exacerbate pulmonary immunopathology including eosinophilic infiltration in the lungs after an RSV challenge in animal models, raising concerns about enhanced respiratory disease (ERD); thus, approaches that mitigate these effects are urgently needed. Herein, we aimed to examine the mechanisms of G protein vaccine-induced ERD in mice, using recombinant G protein as a vaccine antigen. After the RSV challenge, G protein-vaccinated mice exhibited lung weight gain, lung tissue damage, and increased infiltration of eosinophils, neutrophils, and CD4+ T cells into the lungs. We set lung weight gain as the endpoint for ERD and examined the impact of each infiltrating cell on lung weight gain. We observed that CD4+ T cells, but not eosinophils or neutrophils, that infiltrate the lungs are responsible for lung weight gain. In addition, T helper 2 cell-mediated IL-13 induced mucin hypersecretion and lung weight gain. Mucin hypersecretion may contribute to weight gain in the lungs. In conclusion, our results indicate a novel mechanism of G protein vaccine-induced ERD via IL-13 and mucin hypersecretion, which could lead to the development of safe G protein vaccines and the elucidation of the causes of ERD associated with other vaccines.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	98546
citation_title	Recombinant RSV G protein vaccine induces enhanced respiratory disease via IL-13 and mucin overproduction
citation_author	Kawahara, Eigo
	Senpuku, Kota
	Kawaguchi, Yoshino
	Yamamoto, Shinya
	Yasuda, Koubun
	Kuroda, Etsushi
	Ouji-Sageshima, Noriko
	Ito, Toshihiro
	Hirai, Toshiro
	Shibata, Takehiko
	Yoshioka, Yasuo
citation_publisher	Nature Research
citation_language	English
citation_date	2024-10-12
citation_journal_title	npj Vaccines
citation_volume	9
citation_firstpage	187
citation_doi	https://doi.org/10.1038/S41541-024-00987-W
citation_public_url	https://hdl.handle.net/11094/98546

Recombinant RSV G protein vaccine induces enhanced respiratory disease via IL-13 and mucin overproduction

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