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論文
タイトル
タイトル(英)
Carrier-free mRNA vaccine induces robust immunity against SARS-CoV-2 in mice and non-human primates without systemic reactogenicity.
参照URL
https://researchmap.jp/read0088287/published_papers/46131395
著者
著者(英)
Saed Abbasi,Miki Matsui-Masai,Fumihiko Yasui,Akimasa Hayashi,Theofilus A Tockary,Yuki Mochida,Shiro Akinaga,Michinori Kohara,Kazunori Kataoka,Satoshi Uchida
担当区分
概要
概要(英)
Carrier-free naked mRNA vaccines may reduce the reactogenicity associated with delivery carriers; however, their effectiveness against infectious diseases has been suboptimal. To boost efficacy, we targeted the skin layer rich in antigen-presenting cells (APCs) and utilized a jet injector. The jet injection efficiently introduced naked mRNA into skin cells, including APCs in mice. Further analyses indicated that APCs, after taking up antigen mRNA in the skin, migrated to the lymph nodes (LNs) for antigen presentation. Additionally, the jet injection provoked localized lymphocyte infiltration in the skin, serving as a physical adjuvant for vaccination. Without a delivery carrier, our approach confined mRNA distribution to the injection site, preventing systemic mRNA leakage and associated systemic proinflammatory reactions. In mouse vaccination, the naked mRNA jet injection elicited robust antigen-specific antibody production over 6 months, along with germinal center formation in LNs and the induction of both CD4- and CD8-positive T cells. By targeting the SARS-CoV-2 spike protein, this approach provided protection against viral challenge. Furthermore, our approach generated neutralizing antibodies against SARS-CoV-2 in non-human primates at levels comparable to those observed in mice. In conclusion, our approach offers a safe and effective option for mRNA vaccines targeting infectious diseases.
出版者・発行元
出版者・発行元(英)
誌名
誌名(英)
Molecular therapy : the journal of the American Society of Gene Therapy
開始ページ
終了ページ
出版年月
2024年3月22日
査読の有無
招待の有無
掲載種別
研究論文(学術雑誌)
ISSN
DOI URL
https://doi.org/10.1016/j.ymthe.2024.03.022
共同研究・競争的資金等の研究課題
研究者
安井 文彦 (ヤスイ フミヒコ)