A synthetic triacylated pseudo-dipeptide molecule promotes Th1/TReg immune responses and enhances tolerance induction via the sublingual route

Vaccine. 2007 Dec 21;26(1):108-18. doi: 10.1016/j.vaccine.2007.10.050. Epub 2007 Nov 9.

Abstract

In this study, we tested two triacylated pseudo-dipeptidic molecules, OM-197-MP-AC and OM-294-BA-MP as candidate adjuvants for allergy vaccines. Both molecules induce human dendritic cell (h-DC) maturation and polarize naïve T cells toward the Th1 type with IFNgamma production. Only OM-294-BA-MP induces IL10 gene expression both in monocyte-derived DCs and CD4+ naïve T cells. Sublingual administration of OM-294-BA-MP plus the antigen enhances tolerance induction in BALB/c mice with established asthma to ovalbumin with an impact on both airways hyperresponsiveness and lung inflammation. Given its Th1/Treg polarizing properties, OM-294-BA-MP is a valid candidate for sublingual allergy vaccines.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Administration, Sublingual
  • Animals
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / physiology
  • Cell Polarity
  • Dendritic Cells / drug effects
  • Dendritic Cells / physiology
  • Desensitization, Immunologic / methods*
  • Dipeptides / pharmacology*
  • Female
  • Humans
  • Immune Tolerance*
  • Interferon-gamma / biosynthesis
  • Mice
  • Mice, Inbred BALB C
  • T-Lymphocytes, Regulatory / immunology*
  • Th1 Cells / immunology*

Substances

  • Adjuvants, Immunologic
  • Dipeptides
  • Interferon-gamma