2026-07-18 東京大学,東京理科大学

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脂質ナノ粒子をベースとしたmRNAワクチンでは、特異的な抗原提示経路が強力なT細胞免疫を誘導する A distinct antigen presentation pathway drives potent T cell immunity in lipid nanoparticle–based mRNA vaccines
Ryunosuke Muro, Suqi Wang, Taku Ito-Kureha, Hung Hiep Huynh, […] , and Hiroshi Takayanagi
Science Advances Published:17 Jul 2026
DOI:https://doi.org/10.1126/sciadv.aec7827
Abstract
Lipid nanoparticle–encapsulated mRNA (mRNA-LNP) vaccines trigger the potent differentiation of antigen-specific cytotoxic CD8 T cells in addition to antibody production. Despite its high immunogenicity, the cellular mechanisms by which mRNA-LNP induces such unusual immune responses remain largely unclear. Here, we show that mRNA-LNP induces potent and long-lasting CD8 T cell expansion through an antigen presentation mechanism that differs from that of conventional adjuvants. In mice immunized with mRNA-LNP, the number of antigen-specific CD8 T cells was one order of magnitude higher than that induced by combining antigen proteins with immunostimulants such as lipopolysaccharide or polyinosinic:polycytidinic acid. Intramuscularly administered mRNA-LNPs were mainly taken up by migratory type 2 conventional dendritic cells in draining lymph nodes, resulting in notably strong and persistent antigen presentation through major histocompatibility complex class I. Furthermore, CD8 T cell induction by mRNA-LNP required migratory dendritic cells but not the traditional cross-presentation pathway that is otherwise essential for antiviral and antitumor immunity. Thus, the mRNA-LNP formulation exerts unconventional immune responses through a different antigen-presentation pathway from conventional component vaccines.

