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A palindromic CpG-containing phosphodiester oligodeoxynucleotide as a mucosal adjuvant stimulates plasmacytoid

Jun-ichi Maeyama1, Hisakazu Takatsuka2, Fumiko Suzuki3

  • 1Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo, Japan.

Plos One
|March 4, 2014
PubMed
Abstract

Insights

A novel CpG oligodeoxynucleotide (ODN), G9.1, effectively induces plasmacytoid dendritic cell (pDC)-mediated T(H)1 immunity via mucosal vaccination, showing promise as a new vaccine adjuvant.

Area of Science:

  • Immunology
  • Vaccinology
  • Molecular Biology

Background:

  • CpG oligodeoxynucleotides (ODNs) are investigated as vaccine adjuvants, with immune responses varying by sequence and administration.
  • Developing CpG ODNs for mucosal T(H)1 immunity induction via plasmacytoid dendritic cells (pDCs) is a key research area.

Purpose of the Study:

  • To create a novel phosphodiester CpG ODN, G9.1, with properties enabling pDC-mediated mucosal T(H)1 immunity.
  • To assess G9.1's capacity for inducing T(H)1 immune responses through mucosal administration.

Main Methods:

  • Evaluated T(H)1/T(H)2 immunity using cytokine profiles and T-bet/GATA-3 ratios in human and mouse cells.
  • Assessed adjuvanticity of G9.1 with diphtheria toxoid (DT) via nasal vaccination in mice.

Main Results:

  • G9.1 demonstrated superior IFN-α induction and enhanced T-bet expression compared to A-class CpG ODN2216.
  • Nasal G9.1 plus DT induced specific mucosal IgA and serum IgG with antitoxin activity, dependent on pDCs for T(H)1 responses.

Conclusions:

  • G9.1 is a promising candidate for a mucosal adjuvant.
  • G9.1 facilitates pDC-mediated T(H)1 immunity induction.
  • The study provides the first in vivo evidence of CpG ODN-mediated T(H)1 antibody induction dependent on pDCs.

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