Efficient immunogenic peptide antigen delivery to dendritic cells using an ESCRT-mediated extracellular vesicle formation method
2021
Kimura, Sakika | Maeda, Koki | Nagashima, Ryuichi | Miura, Koya | Arakawa, Masashi | Ebina, Hirotaka | Tanaka, Nobuyuki | Morita, Eiji
In the activation of cell-mediated adaptive immune responses that play major roles in the elimination of virus-infected or tumor cells, it is important that dendritic cells present antigen peptides on major histocompatibility complex (MHC) class I molecules and activate pathogen-specific cytotoxic T lymphocytes (CTL). As exogenous peptide antigens are generally presented on MHC class II but not class I, the development of a method for exogenous antigen delivery that facilitates MHC class I presentation is necessary for a potentially effective vaccine that is expected to provoke cell-mediated adaptive immune responses. Here, we developed extracellular vesicles that incorporate antigenic proteins by utilizing endosomal sorting complexes required for transport (ESCRT)-mediated vesicle formation pathway. Furthermore, we proved that these vesicles could deliver their contents to the cytoplasm of dendritic cells and activate antigen-specific CTLs. These technologies could be applied to the development of novel CTL-inducing peptide vaccines.
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