Transdermal immunization using solid-in-oil nanodispersion with CpG oligodeoxynucleotide adjuvants

Pharm Res. 2015 Apr;32(4):1486-92. doi: 10.1007/s11095-014-1554-5. Epub 2014 Nov 1.

Abstract

Purpose: Simple and noninvasive vaccine administration alternatives to injections are desired. A solid-in-oil (S/O) nanodispersion system was able to overcome skin barriers and induce an immune response; however, antibody levels remained low. We applied an immune potentiator, CpG oligodeoxynucleotide (ODN), to enhance the immune response by controlling the T helper 1 (Th1)/T helper 2 (Th2) balance.

Methods: S/O nanodispersions containing ovalbumin (OVA) and CpG ODN (CpG-A or CpG-B) were characterized by size distribution analysis and a protein release test. The skin permeation of fluorescence-labeled OVA was observed by fluorescence microscopy. Antigen-specific IgG, IgG1, and IgG2a responses were measured by enzyme-linked immunosorbent assay.

Results: Co-encapsulation of CpG ODNs in S/O nanodispersions enhanced induction of OVA-specific IgG. S/O nanodispersion containing OVA and CpG-A had a smaller mean particle size and permeated the skin more efficiently. In contrast, CpG-B showed the highest protein release and induction of OVA-specific IgG. IgG subclass analysis revealed that OVA induced a Th2-dominant immune response, while the S/O nanodispersion containing CpG-A skewed the immune response toward a Th1-bias.

Conclusions: In combination with CpG ODN, the S/O nanodispersion system efficiently induced an antigen-specific antibody response. The Th1/Th2 immune balance could be controlled by the selection of CpG ODN type.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Administration, Cutaneous
  • Animals
  • Emulsions
  • Immunization / methods*
  • Immunoglobulin G / blood
  • Male
  • Mice, Inbred Strains
  • Nanoparticles / chemistry*
  • Oligodeoxyribonucleotides / administration & dosage*
  • Oligodeoxyribonucleotides / immunology
  • Ovalbumin / administration & dosage*
  • Ovalbumin / immunology
  • Vaccines / administration & dosage*
  • Vaccines / immunology

Substances

  • Adjuvants, Immunologic
  • CPG-oligonucleotide
  • Emulsions
  • Immunoglobulin G
  • Oligodeoxyribonucleotides
  • Vaccines
  • Ovalbumin