| 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 |
| vaccine |
| 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 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/86168 |
| 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)
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