Activation of antigen-specific T cell-responses by mannan-decorated PLGA nanoparticles

Pharm Res. 2011 Sep;28(9):2288-301. doi: 10.1007/s11095-011-0459-9. Epub 2011 May 11.

Abstract

Purpose: Mannosylation of vaccines is a promising strategy to selectively target vaccine antigens to the mannose receptor expressed on dendritic cells (DCs). The purpose of this study was to investigate the effect of mannan (MN) chemically conjugated to poly(D, L-lactide-co-glycolic acid) (PLGA) nanoparticles (NPs) on antigen-specific T-cell responses elicited by a model antigen (ovalbumin, OVA) loaded in PLGA-NPs.

Methods: In vitro T-cell proliferation assay was done to assess the ability of DCs treated with OVA-NPs (±MN decoration) to induce antigen-specific T-cell activation. The efficacy of this vaccination strategy was further evaluated in vivo, where T-cell proliferation was performed to evaluate activation of T-cell responses in lymph nodes and spleens isolated from the vaccinated mice.

Results: Our results demonstrate that MN-decorated antigen-loaded PLGA-NPs simultaneously enhanced antigen-specific CD4+ and CD8+ T-cell responses compared to non-decorated NPs.

Conclusions: MN decoration of PLGA-NPs is a promising strategy for enhancing antigen-specific T-cell responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / administration & dosage*
  • Antigens / immunology
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Proliferation / drug effects
  • Dendritic Cells / immunology
  • Drug Carriers / chemistry*
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class II / genetics
  • Lactic Acid / chemistry*
  • Lectins, C-Type / immunology
  • Lymph Nodes / drug effects
  • Lymph Nodes / immunology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Male
  • Mannans / chemistry*
  • Mannose Receptor
  • Mannose-Binding Lectins / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Receptors, Cell Surface / immunology
  • Spleen / drug effects
  • Spleen / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Vaccines / administration & dosage*
  • Vaccines / immunology

Substances

  • Antigens
  • Drug Carriers
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Lectins, C-Type
  • Mannans
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • Vaccines
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Ovalbumin