Novel vaccine delivery system induces robust humoral and cellular immune responses based on multiple mechanisms

Adv Healthc Mater. 2014 May;3(5):670-81. doi: 10.1002/adhm.201300335. Epub 2013 Nov 6.

Abstract

Aiming to enhance the immunogenicity of H5N1 split vaccine, the development of a novel antigen delivery system based on quaternized chitosan hydrogel microparticles (Gel MPs) with multiple mechanisms of immunity enhancement is attempted. Gel MPs based on ionic cross-linking are prepared in a simple and mild way. Gel MPs are superior as a vaccine delivery system due to their ability to: 1) enhance cellular uptake and endosomal escape of antigens in dendritic cells (DCs); 2) significantly activate DCs; 3) form an antigen depot and recruit immunity cells to improve antigen capture. Further in vivo investigation shows that Gel MPs, in comparison to aluminum salts (Alum), LPS, and covalent cross-linking quaternized chitosan MPs (GC MPs), induce higher humoral and cellular immune responses with a mixed Th1/Th2 immunity. In conclusion, these results demonstrate that Gel MPs are efficient antigen delivery vehicles based on multiple mechanisms to enhance both humoral and cellular immune responses against H5N1 split antigen.

Keywords: H5N1 split vaccines; adjuvants; hydrogels; particulate delivery system; quaternized chitosan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Chitosan / chemistry
  • Drug Delivery Systems*
  • Erythrocytes / pathology
  • Hemolysis
  • Humans
  • Hydrogels / chemistry
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / chemistry
  • Influenza Vaccines / immunology*
  • Influenza Vaccines / pharmacokinetics
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control
  • Sheep

Substances

  • Antibodies, Viral
  • Hydrogels
  • Influenza Vaccines
  • Chitosan