Sugar-Nanocapsules Imprinted with Microbial Molecular Patterns for mRNA Vaccination

Nano Lett. 2020 Mar 11;20(3):1499-1509. doi: 10.1021/acs.nanolett.9b03483. Epub 2020 Feb 10.

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.

Keywords: dendritic cell; mRNA; nanoparticle; polysaccharide; vaccine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Cancer Vaccines* / chemistry
  • Cancer Vaccines* / pharmacology
  • Dendritic Cells / immunology*
  • Dendritic Cells / pathology
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Mice
  • Nanocapsules* / chemistry
  • Nanocapsules* / therapeutic use
  • Neoplasms, Experimental* / immunology
  • Neoplasms, Experimental* / pathology
  • Neoplasms, Experimental* / therapy
  • Polysaccharides, Bacterial* / chemistry
  • Polysaccharides, Bacterial* / pharmacology
  • RNA, Messenger* / chemistry
  • RNA, Messenger* / pharmacology
  • Vaccination*

Substances

  • Cancer Vaccines
  • Nanocapsules
  • Polysaccharides, Bacterial
  • RNA, Messenger