Comparative activity of biodegradable nanoparticles with aluminum adjuvants: antigen uptake by dendritic cells and induction of immune response in mice

Immunol Lett. 2011 Oct 30;140(1-2):36-43. doi: 10.1016/j.imlet.2011.06.002. Epub 2011 Jun 12.

Abstract

Biodegradable poly(γ-glutamic acid) (γ-PGA) nanoparticles (NPs) are considered to be an excellent antigen carrier. Antigen-carrying γ-PGA NPs were examined for their uptake by murine dendritic cells (DCs) and subsequent induction of antigen-specific immune responses in mice and compared with aluminum (AL) adjuvants. Ovalbumin (OVA)-carrying NPs (FITC-OVA-NPs) were taken up much more efficiently by DCs than OVA alone or its AL-associated form. Both OVA-NPs and OVA+AL were detected in an intracellular lysosome compartment of DCs. Furthermore, the uptake of γ-PGA NPs was inhibited in the presence of pinocytosis and phagocytosis inhibitors. Significantly higher induction of antigen-specific CD8(+) T cells was observed in mice immunized with OVA-carrying γ-PGA NPs than in those immunized with OVA alone, OVA+AL, OVA+3-O-desacyl-4'-monophosphoryl lipid A (MPL), and OVA+AL+MPL. Thus, γ-PGA NPs may have great potential as an effective vaccine carrier and adjuvant for clinical use.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorbable Implants / statistics & numerical data
  • Adjuvants, Immunologic / administration & dosage*
  • Aluminum / administration & dosage*
  • Animals
  • Antigens / immunology
  • Antigens / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / pathology
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Dendritic Cells / pathology
  • Endocytosis / immunology
  • Female
  • Immunity, Cellular
  • Immunization
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Ovalbumin / immunology
  • Ovalbumin / metabolism
  • Polyglutamic Acid / analogs & derivatives
  • Polyglutamic Acid / chemistry

Substances

  • Adjuvants, Immunologic
  • Antigens
  • poly(gamma-glutamic acid)
  • Polyglutamic Acid
  • Ovalbumin
  • Aluminum