Sugar-Nanocapsules Imprinted with Microbial Molecular Patterns for mRNA Vaccination

印有微生物分子模式的糖纳米胶囊可用于 mRNA 疫苗接种

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作者:Sejin Son, Jutaek Nam, Ilia Zenkov, Lukasz J Ochyl, Yao Xu, Lindsay Scheetz, Jinjun Shi, Omid C Farokhzad, James J Moon

Abstract

Innate immune cells recognize and respond to pathogen-associated molecular patterns. In particular, polysaccharides found in the microbial cell wall are potent activators of dendritic cells (DCs). Here, we report a new class of nanocapsules, termed sugar-capsules, entirely composed of polysaccharides derived from the microbial cell wall. We show that sugar-capsules with a flexible polysaccharide shell and a hollow core efficiently drain to lymph nodes and activate DCs. In particular, sugar-capsules composed of mannan (Mann-capsule) carrying mRNA (mRNA) promote strong DC activation, mRNA translation, and antigen presentation on DCs. Mann-capsules elicit robust antigen-specific CD4+ and CD8α+ T-cell responses with antitumor efficacy in vivo. The strategy presented in this study is generally applicable for utilizing pathogen-derived molecular patterns for vaccines and immunotherapies.

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