2026-10-27 東京科学大学
無針のジェット投与により、皮下へmRNAワクチンを接種
＜関連情報＞
複数のアジュバントと組み合わせたジェットインジェクション法による裸のmRNAワクチンの接種は、マウスにおける呼吸器ウイルス感染症に対する防御効果を増強する Jet-injected combinational adjuvants potentiate naked mRNA vaccines for protection against respiratory viral infections in mice
Nan Qiao, Junichi Ishikawa, Fumihiko Yasui, Kaori Sano, Kei Miyakawa, Akimasa Hayashi, Ahmad Faisal Amiry, Haonan Liu, Xueyang Zhu, Naoko Takeda-Miyata, Motohiro Kojima, Taku Sato, Renata Pasqualini, Wadih Arap, Kazunori Kataoka, Hideki Hasegawa, Michinori Kohara, and Satoshi Uchida
Journal of Clinical Investigation Published: October 20, 2026
DOI:https://doi.org/10.1172/JCI204021
Abstract
The use of lipid nanoparticles (LNPs) to enhance delivery and immunogenicity of mRNA vaccines raises safety concerns due to strong reactogenicity. Developing naked mRNA vaccines, which can be delivered through liquid jet-injection to the skin, may offer a safer alternative, but their immunogenicity has been limited. To address this challenge, we screened clinically relevant adjuvants to enhance the efficacy of N1-methyl-pseudouridine-modified naked mRNA jet-injection vaccines in mouse models. Although many adjuvants showed little or inhibitory effects on inducing humoral or cellular immunity—despite their known ability to potentiate conventional non-mRNA vaccine platforms—we identified a combination of aluminum phosphate and CpG oligonucleotide that substantially enhanced both humoral and cellular immune responses with increased IgG2a/IgG1 ratio. This adjuvanted naked mRNA vaccine induced IgG2a and cellular immunity at levels comparable to those achieved with LNPs but with lower local and systemic reactogenicity. Mechanistic investigations revealed key roles for type I interferon and interleukin-6 signaling during immunization. Notably, this vaccine formulation in mice virtually eliminated infection by both SARS-CoV-2 and influenza A virus (A/California/7/2009 H1N1) in plaque-forming assays. Collectively, the adjuvanted naked mRNA jet-injection vaccine represents an effective, and safe platform against infectious diseases, with potential for clinic-ready translational applications.
