Ken Ishii on Muck Rack

Ken Ishii

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Articles

A poorly reactogenic lipid nanoparticle-mRNA vaccine unveils an innate immune pathway for adverse reactions

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By Tomohiro Takano, Keigo Kumagai, Hitoshi Iuchi, Kazutaka Terahara, Aya Mizuike, Eita Sasaki, Yu Adachi, Ryutaro Kotaki, Saya Moriyama, Shinichiro Ota, Kyoko Saito, Masanori Isogawa, Kohei Soga, Haruyo Nakajima-Adachi, Satoshi Hachimura, Kouji Kobiyama, Ken Ishii, Michiaki Hamada, Masayoshi Fukasawa, Masaharu Shinkai, Takayuki Matsumura, Yoshimasa Takahashi, Mizuki Fujisawa, Tomoharu Mizukami
| Nature Verified
Abstract Lipid nanoparticle (LNP)-mRNA vaccines robustly activate immune responses, contributing to their high efficacy and frequent adverse reactions (ARs). Here, we identified an LNP-mRNA formulation with a more favorable balanced immunogenicity-reactogenicity profile. Immune profiling in a mouse model defined the reactogenic LNP-mRNA vaccine as a potent inducer of HMGB1 release, pro-inflammatory cytokine production, and concurrent neutrophil infiltration.
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IL-1 delineates squalene-based adjuvant efficacy and reactogenicity in a cell-type-specific manner

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By Kouji Kobiyama, Tomoya Hayashi, Yujiro Kidani, Akimasa Yoshimura, Motoyasu Onishi, Takayuki Nakagawa, Satoru Ishida, Cevayir Coban, Ken Ishii, Yuya Yoshioka, Anri Nishinaka-Yoshioka, Yosuke Yanagida, Junpei Kasahara, Kenichiro Tsujii, Yoshiji Asaoka, Norikazu Kuroda, Akira Kugimiya, Hiroaki Osawa, Shinya Omoto, Morio Nagira
| Nature Verified
Abstract Squalene-based adjuvants are widely utilized in various vaccines because of their effectiveness in enhancing immune responses. Among these, A-910823 and AS03 are recognized squalene-based adjuvants containing α-tocopherol. Although α-tocopherol-containing squalene-based adjuvants are known to enhance humoral immune responses and inflammatory cytokine production, their underlying mechanisms remain unclear.
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cGAS-IFN-I responses by extracting nuclear DNA from dying cells via nucleocytosis - Nature Communications

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By Hideo Negishi, Yusuke Wada, Yoshitaka Shirasaki, Tomoya Hayashi, Yuji Kubota, Tomio Iwasaki, Mina Kurosawa, Tatsuma Ban, Daisuke Muto, Yusuke Suenaga, Taichi Kojima, Yuzuki Matsuda, Sean Irish, Kosuke Dodo, Toru Suzuki, Mai Yamagishi, Burcu Temizoz, Atsushi Yoshimori, Chisato Kanai, Yoji Nagasaki, Masaki Ohmuraya, Tomohiko Tamura, Atsushi Iwama, Toshifumi Inada, Etsushi Kuroda, Kouji Kobiyama, Noriko Toyama-Sorimachi, Mutsuhiro Takekawa, Cevayir Coban, Ken Ishii
| Nature Verified
Abstract Self-DNA triggers cGAS-STING-mediated type I interferon (IFN-I) to induce both protective and pathogenic immune responses; however, how self-DNA activates the cytosolic cGAS-STING pathway remains unclear. Here we show that the cGAS/STING/IFN-I axis is activated by self-DNA via a process termed ‘nucleocytosis’, in which nuclear DNA is extracted from dying cells by macrophages.
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