Potent priming by inactivated whole influenza virus particle vaccines is linked to viral RNA uptake into antigen presenting cells

Shingai, Masashi; Nomura, Naoki; Sekiya, Toshiki; Ohno, Marumi; Fujikura, Daisuke; Handabile, Chimuka; Omori, Ryosuke; Ohara, Yuki; Nishimura, Tomohiro; Endo, Masafumi; Kimachi, Kazuhiko; Mitsumata, Ryotarou; Ikeda, Tomio; Kitayama, Hiroki; Hatanaka, Hironori; Sobue, Tomoyoshi; Muro, Fumihito; Suzuki, Saori; Nguyen, Cong Thanh; Ishigaki, Hirohito; Nakayama, Misako; Mori, Yuya; Itoh, Yasushi; Koutsakos, Marios; Chua, Brendon Y.; Brown, Lorena E.; Jackson, David C.; Kedzierska, Katherine; Ogasawara, Kazumasa; Kino, Yoichiro; Kida, Hiroshi

Potent priming by inactivated whole influenza virus particle vaccines is linked to viral RNA uptake into antigen presenting cells

Shingai, Masashi; Nomura, Naoki; Sekiya, Toshiki et al.

Vaccine, 2021, 39(29), 3940-3951

Permalink : https://hdl.handle.net/2115/86168

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アクセス権	open access
URI	https://hdl.handle.net/2115/86168
タイトル	Potent priming by inactivated whole influenza virus particle vaccines is linked to viral RNA uptake into antigen presenting cells
著者	Shingai, Masashi ; Nomura, Naoki ; Sekiya, Toshiki ; Ohno, Marumi ; Fujikura, Daisuke ; Handabile, Chimuka ; Omori, Ryosuke ; Ohara, Yuki ; Nishimura, Tomohiro ; Endo, Masafumi ; Kimachi, Kazuhiko ; Mitsumata, Ryotarou ; Ikeda, Tomio ; Kitayama, Hiroki ; Hatanaka, Hironori ; Sobue, Tomoyoshi ; Muro, Fumihito ; Suzuki, Saori ; Nguyen, Cong Thanh ; Ishigaki, Hirohito ; Nakayama, Misako ; Mori, Yuya ; Itoh, Yasushi ; Koutsakos, Marios ; Chua, Brendon Y. ; Brown, Lorena E. ; Jackson, David C. ; Kedzierska, Katherine ; Ogasawara, Kazumasa ; Kino, Yoichiro ; Kida, Hiroshi
e-Rad_Researcher 80421981 著者名 Shingai, Masashi
著者名 Nomura, Naoki
著者名 Sekiya, Toshiki
e-Rad_Researcher 50794202 著者名 Ohno, Marumi
著者名 Fujikura, Daisuke
著者名 Handabile, Chimuka
e-Rad_Researcher 10746952 著者名 Omori, Ryosuke
著者名 Ohara, Yuki
著者名 Nishimura, Tomohiro
著者名 Endo, Masafumi
著者名 Kimachi, Kazuhiko
著者名 Mitsumata, Ryotarou
著者名 Ikeda, Tomio
著者名 Kitayama, Hiroki
著者名 Hatanaka, Hironori
著者名 Sobue, Tomoyoshi
著者名 Muro, Fumihito
著者名 Suzuki, Saori
著者名 Nguyen, Cong Thanh
著者名 Ishigaki, Hirohito
著者名 Nakayama, Misako
著者名 Mori, Yuya
著者名 Itoh, Yasushi
著者名 Koutsakos, Marios
著者名 Chua, Brendon Y.
著者名 Brown, Lorena E.
著者名 Jackson, David C.
著者名 Kedzierska, Katherine
著者名 Ogasawara, Kazumasa
著者名 Kino, Yoichiro
e-Rad_Researcher 10109506 著者名 Kida, Hiroshi
言語	英語
キーワード	Inactivated whole influenza virus particle
	vaccine
	Seasonal and pandemic influenza
発行日	2021-06-29
出版者	Elsevier
収録物名	Vaccine
巻(号)	39(29)
ページ	3940-3951
抄録	Current detergent or ether-disrupted split vaccines (SVs) for influenza do not always induce adequate immune responses, especially in young children. This contrasts with the whole virus particle vaccines (WPVs) originally used against influenza that were immunogenic in both adults and children but were replaced by SV in the 1970s due to concerns with reactogenicity. In this study, we re-evaluated the immunogenicity of WPV and SV, prepared from the same batch of purified influenza virus, in cynomolgus macaques and confirmed that WPV is superior to SV in priming potency. In addition, we compared the ability of WPV and SV to induce innate immune responses, including the maturation of dendritic cells (DCs) in vitro. WPV stimulated greater production of inflammatory cytokines and type-I interferon in immune cells from mice and macaques compared to SV. Since these innate responses are likely triggered by the activation of pattern recognition receptors (PRRs) by viral RNA, the quantity and quality of viral RNA in each vaccine were assessed. Although the quantity of viral RNA was similar in the two vaccines, the amount of viral RNA of a length that can be recognized by PRRs was over 100-fold greater in WPV than in SV. More importantly, 1000-fold more viral RNA was delivered to DCs by WPV than by SV when exposed to preparations containing the same amount of HA protein. Furthermore, WPV induced up regulation of the DC maturation marker CD86 on murine DCs, while SV did not. The present results suggest that the activation of antigen-presenting DCs, by PRR-recognizable viral RNA contained in WPV is responsible for the effective priming potency of WPV observed in naive mice and macaques. WPV is thus recommended as an alternative option for seasonal influenza vaccines, especially for children. (c) 2021 Elsevier Ltd. All rights reserved.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	© 2021. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	0264-410X
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.vaccine.2021.05.065