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

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Title: Potent priming by inactivated whole influenza virus particle vaccines is linked to viral RNA uptake into antigen presenting cells
Authors: Shingai, Masashi Browse this author →KAKEN DB
Nomura, Naoki Browse this author
Sekiya, Toshiki Browse this author
Ohno, Marumi Browse this author →KAKEN DB
Fujikura, Daisuke Browse this author
Handabile, Chimuka Browse this author
Omori, Ryosuke Browse this author →KAKEN DB
Ohara, Yuki Browse this author
Nishimura, Tomohiro Browse this author
Endo, Masafumi Browse this author
Kimachi, Kazuhiko Browse this author
Mitsumata, Ryotarou Browse this author
Ikeda, Tomio Browse this author
Kitayama, Hiroki Browse this author
Hatanaka, Hironori Browse this author
Sobue, Tomoyoshi Browse this author
Muro, Fumihito Browse this author
Suzuki, Saori Browse this author
Nguyen, Cong Thanh Browse this author
Ishigaki, Hirohito Browse this author
Nakayama, Misako Browse this author
Mori, Yuya Browse this author
Itoh, Yasushi Browse this author
Koutsakos, Marios Browse this author
Chua, Brendon Y. Browse this author
Brown, Lorena E. Browse this author
Jackson, David C. Browse this author
Kedzierska, Katherine Browse this author
Ogasawara, Kazumasa Browse this author
Kino, Yoichiro Browse this author
Kida, Hiroshi Browse this author →KAKEN DB
Keywords: Inactivated whole influenza virus particle
Seasonal and pandemic influenza
Issue Date: 29-Jun-2021
Publisher: Elsevier
Journal Title: Vaccine
Volume: 39
Issue: 29
Start Page: 3940
End Page: 3951
Publisher DOI: 10.1016/j.vaccine.2021.05.065
Abstract: 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.
Rights: © 2021. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Type: article (author version)
Appears in Collections:人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 喜田 宏

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