Comparative immunogenic and structural analysis of virus-like particle and inactivated whole-virion vaccines against enterovirus D68

Senpuku, Kota; Kunishima, Yuta; Hirose, Mika; Karaki, Tatsuya; Taniguchi, Kotaro; Kataoka-Nakamura, Chikako; Hirai, Toshiro; Yasuda, Koubun; Kuroda, Etsushi; Kato, Takayuki; Ito, Taiki; Yoshioka, Yasuo

doi:https://doi.org/10.1016/j.omtn.2026.102957

Comparative immunogenic and structural analysis of virus-like particle and inactivated whole-virion vaccines against enterovirus D68

Senpuku, Kota; Kunishima, Yuta; Hirose, Mika et al.

Molecular Therapy Nucleic Acids, 2026, 37(2), 102957

Number of Access:219（2026-10-28 15:26 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/106763

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Title	Comparative immunogenic and structural analysis of virus-like particle and inactivated whole-virion vaccines against enterovirus D68
Creator	CreatorName Senpuku, Kota
	CreatorName Kunishima, Yuta
	ORCID 0000-0001-8991-587X 0000-0001-8991-587X researchmap permalink mhiro_map mhiro_map Scopus Author ID 55672764900 55672764900 CreatorName Hirose, Mika
	CreatorName Karaki, Tatsuya
	CreatorName Taniguchi, Kotaro
	NRID 1000010646623 1000010646623 CreatorName Kataoka-Nakamura, Chikako
	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 1000050333539 1000050333539 CreatorName Yasuda, Koubun
	NRID 1000010299604 1000010299604 CreatorName Kuroda, Etsushi
	NRID 1000020423155 1000020423155 ORCID 0000-0002-8879-6685 0000-0002-8879-6685 researchmap permalink tkato_ipr tkato_ipr Scopus Author ID 55261010900 55261010900 CreatorName Kato, Takayuki
	NRID 1000081019818 1000081019818 ORCID 0000-0002-1408-7288 0000-0002-1408-7288 researchmap permalink ito_taiki ito_taiki CreatorName Ito, Taiki
	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	cryo-electron microscopy
	enterovirus D68
	epitope
	inactivated whole-virion
	MT: delivery strategies
	virus-like particle
Description	Senpuku K., Kunishima Y., Hirose M., et al. Comparative immunogenic and structural analysis of virus-like particle and inactivated whole-virion vaccines against enterovirus D68. Molecular Therapy Nucleic Acids 37(2), 102957 (2026); https://doi.org/10.1016/j.omtn.2026.102957.
Abstract	Enterovirus D68 (EV-D68) primarily causes respiratory illnesses and has been implicated in acute flaccid myelitis. Although virus-like particle (VLP) and traditional inactivated whole-virion (IWV) vaccines have demonstrated efficacy in mice, their immunological differences remain undetermined. Here, we directly compared the immunogenic and structural properties of VLP and IWV vaccines derived from the same EV-D68 strain under identical conditions. Although VLP induced significantly lower levels of EV-D68-specific IgG than IWV, neutralizing antibody titers and protective effects against viral challenge were comparable between the two groups in mice. Passive transfer experiments in neonatal mice further confirmed protection against lethal infection for both vaccine groups. Notably, in contrast to the IWV vaccine, the VLP vaccine elicited antibodies that preferentially recognized a limited subset of epitopes. Cryo-electron microscopy analyses revealed that VLPs structurally resemble the native virus but display distinct features in regions corresponding to epitopes that show differential antibody reactivity between VLP and IWV vaccines. By integrating structural and immunological analyses, we established a mechanistic framework linking capsid architecture to vaccine-induced antibody specificity. These findings suggest that VLP is a promising EV-D68 vaccine antigen with distinct epitope recognition profiles driven by structural characteristics.
Publisher	Cell Press
Source Title	Molecular Therapy Nucleic Acids
Volume (Issue)	37(2)
Page	102957
Date of Issued	2026-06-08
Language	English
Handle URL	https://hdl.handle.net/11094/106763
eISSN	21622531
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1016/j.omtn.2026.102957
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
DCMI Type	Text
DCTERMS.bibliographicCitation	Molecular Therapy Nucleic Acids. 2026, 37(2), p. 102957
DC.title	Comparative immunogenic and structural analysis of virus-like particle and inactivated whole-virion vaccines against enterovirus D68
DC.creator	Senpuku, Kota
	Kunishima, Yuta
	Hirose, Mika
	Karaki, Tatsuya
	Taniguchi, Kotaro
	Kataoka-Nakamura, Chikako
	Hirai, Toshiro
	Yasuda, Koubun
	Kuroda, Etsushi
	Kato, Takayuki
	Ito, Taiki
	Yoshioka, Yasuo
DC.publisher	Cell Press
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2026-06-08
DC.identifier	https://doi.org/10.1016/j.omtn.2026.102957
DC.subject	cryo-electron microscopy
	enterovirus D68
	epitope
	inactivated whole-virion
	MT: delivery strategies
	virus-like particle
DC.description	Senpuku K., Kunishima Y., Hirose M., et al. Comparative immunogenic and structural analysis of virus-like particle and inactivated whole-virion vaccines against enterovirus D68. Molecular Therapy Nucleic Acids 37(2), 102957 (2026); https://doi.org/10.1016/j.omtn.2026.102957.
DCTERMS.abstract	Enterovirus D68 (EV-D68) primarily causes respiratory illnesses and has been implicated in acute flaccid myelitis. Although virus-like particle (VLP) and traditional inactivated whole-virion (IWV) vaccines have demonstrated efficacy in mice, their immunological differences remain undetermined. Here, we directly compared the immunogenic and structural properties of VLP and IWV vaccines derived from the same EV-D68 strain under identical conditions. Although VLP induced significantly lower levels of EV-D68-specific IgG than IWV, neutralizing antibody titers and protective effects against viral challenge were comparable between the two groups in mice. Passive transfer experiments in neonatal mice further confirmed protection against lethal infection for both vaccine groups. Notably, in contrast to the IWV vaccine, the VLP vaccine elicited antibodies that preferentially recognized a limited subset of epitopes. Cryo-electron microscopy analyses revealed that VLPs structurally resemble the native virus but display distinct features in regions corresponding to epitopes that show differential antibody reactivity between VLP and IWV vaccines. By integrating structural and immunological analyses, we established a mechanistic framework linking capsid architecture to vaccine-induced antibody specificity. These findings suggest that VLP is a promising EV-D68 vaccine antigen with distinct epitope recognition profiles driven by structural characteristics.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	106763
citation_title	Comparative immunogenic and structural analysis of virus-like particle and inactivated whole-virion vaccines against enterovirus D68
citation_author	Senpuku, Kota
	Kunishima, Yuta
	Hirose, Mika
	Karaki, Tatsuya
	Taniguchi, Kotaro
	Kataoka-Nakamura, Chikako
	Hirai, Toshiro
	Yasuda, Koubun
	Kuroda, Etsushi
	Kato, Takayuki
	Ito, Taiki
	Yoshioka, Yasuo
citation_publisher	Cell Press
citation_language	English
citation_date	2026-06-08
citation_journal_title	Molecular Therapy Nucleic Acids
citation_volume	37
citation_issue	2
citation_firstpage	102957
citation_doi	https://doi.org/10.1016/j.omtn.2026.102957
citation_public_url	https://hdl.handle.net/11094/106763

Comparative immunogenic and structural analysis of virus-like particle and inactivated whole-virion vaccines against enterovirus D68

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