Near-infrared labeled, ovalbumin loaded polymeric nanoparticles based on a hydrophilic polyester as model vaccine: In vivo tracking and evaluation of antigen-specific CD8(+) T cell immune response

Biomaterials. 2015 Jan:37:469-77. doi: 10.1016/j.biomaterials.2014.10.043. Epub 2014 Oct 28.

Abstract

Particulate antigen delivery systems aimed at the induction of antigen-specific T cells form a promising approach in immunotherapy to replace pharmacokinetically unfavorable soluble antigen formulations. In this study, we developed a delivery system using the model protein antigen ovalbumin (OVA) encapsulated in nanoparticles based on the hydrophilic polyester poly(lactide-co-hydroxymethylglycolic acid) (pLHMGA). Spherical nanoparticles with size 300-400 nm were prepared and characterized and showed a strong ability to deliver antigen to dendritic cells for cross-presentation to antigen-specific T cells in vitro. Using near-infrared (NIR) fluorescent dyes covalently linked to both the nanoparticle and the encapsulated OVA antigen, we tracked the fate of this formulation in mice. We observed that the antigen and the nanoparticles are efficiently co-transported from the injection site to the draining lymph nodes, in a more gradual and durable manner than soluble OVA protein. OVA-loaded pLHMGA nanoparticles efficiently induced antigen cross-presentation to OVA-specific CD8+ T cells in the lymph nodes, superior to soluble OVA vaccination. Together, these data show the potential of pLHMGA nanoparticles as attractive antigen delivery vehicles.

Keywords: Antigen delivery; In vivo tracking; Nanoparticles; Near-infrared imaging; pLHMGA.

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Death
  • Dendritic Cells / metabolism
  • Epitopes
  • Hydrophobic and Hydrophilic Interactions
  • Immunity
  • Infrared Rays*
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Ovalbumin / chemistry*
  • Polyesters / chemical synthesis
  • Polyesters / chemistry*
  • Staining and Labeling*
  • Vaccines / immunology*

Substances

  • Epitopes
  • Polyesters
  • Vaccines
  • poly(lactide-co-hydroxymethyl glycolide)
  • Ovalbumin