Antigen Delivery to Antigen-Presenting Cells for Adaptive Immune Response by Self-Assembled Anionic Polysaccharide Nanogel Vaccines

Biomacromolecules. 2020 Feb 10;21(2):621-629. doi: 10.1021/acs.biomac.9b01351. Epub 2019 Dec 12.

Abstract

Although current vaccine technology induces sufficient antibody responses to prophylactically ward off viral infections, an anticancer vaccine that directs the patient's immune system to directly fight extant malignant cells will require inducing Th1 and cytotoxic T lymphocyte responses in addition to antibody-mediated activities. Thus, new mechanisms are necessary to deliver antigen to cells in the lymphatic system that will induce these responses. To this end, we have developed a cholesterol-bearing pullulan (CHP) self-assembly nanogel of less than 100 nm, which we have now further modified to be anionic by carboxyl group substitution. Overall, the nanogel-protected antigens during transport to the lymphatic system and converting the vehicle to an anionic charge improved interactions with antigen-presenting cells. We further show that these modified nanogels are a more efficient system for delivering antigen to antigen-presenting cells, particularly langerin-expressing cells, and that this induced significant adaptive immunity. Therefore, we think that this technology could be used to improve anticancer immunotherapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / drug effects*
  • Animals
  • Antigen-Presenting Cells / drug effects
  • Antigen-Presenting Cells / immunology*
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Drug Delivery Systems
  • Epitopes
  • Female
  • Immunoglobulin G / blood
  • Lymph Nodes / drug effects
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred C57BL
  • Nanogels / chemistry
  • Ovalbumin / administration & dosage
  • Ovalbumin / pharmacokinetics
  • Polysaccharides / chemistry
  • RAW 264.7 Cells
  • Vaccines / administration & dosage*
  • Vaccines / chemistry*
  • Vaccines / pharmacology

Substances

  • Epitopes
  • Immunoglobulin G
  • Nanogels
  • Polysaccharides
  • Vaccines
  • Ovalbumin