GM-CSF-loaded chitosan hydrogel as an immunoadjuvant enhances antigen-specific immune responses with reduced toxicity

BMC Immunol. 2014 Oct 18:15:48. doi: 10.1186/s12865-014-0048-x.

Abstract

Background: The application of vaccine adjuvants has been vigorously studied for a diverse range of diseases in order to improve immune responses and reduce toxicity. However, most adjuvants have limited uses in clinical practice due to their toxicity.

Methods: Therefore, to reduce health risks associated with the use of such adjuvants, we developed an advanced non-toxic adjuvant utilizing biodegradable chitosan hydrogel (CH-HG) containing ovalbumin (OVA) and granulocyte-macrophage colony-stimulating factor (GM-CSF) as a local antigen delivery system.

Results: After subcutaneous injection into mice, OVA/GM-CSF-loaded CH-HG demonstrated improved safety and enhanced OVA-specific antibody production compared to oil-based adjuvants such as Complete Freund's adjuvant (CFA) or Incomplete Freund's adjuvant (IFA). Moreover, CH-HG system-mediated immune responses was characterized by increased number of OVA-specific CD4(+) and CD8(+) INF-γ(+) T cells, leading to enhanced humoral and cellular immunity.

Conclusions: In this study, the improved safety and enhanced immune response characteristics of our novel adjuvant system suggest the possibility of the extended use of adjuvants in clinical practice with reduced apprehension about toxic side effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / toxicity*
  • Animals
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Chitosan / toxicity*
  • Epitopes / immunology*
  • Female
  • Freund's Adjuvant
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Hydrogel, Polyethylene Glycol Dimethacrylate / toxicity*
  • Immunity / drug effects*
  • Immunization
  • Immunoglobulin G / immunology
  • Injections, Subcutaneous
  • Lipids
  • Mice, Inbred C57BL
  • Ovalbumin / immunology

Substances

  • Adjuvants, Immunologic
  • Epitopes
  • Immunoglobulin G
  • Lipids
  • incomplete Freund's adjuvant
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Ovalbumin
  • Freund's Adjuvant
  • Chitosan