A synthetic triacylated pseudo-dipeptide molecule promotes Th1/TReg immune responses and enhances tolerance induction via the sublingual route.
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.
Mascarell
Laurent
L
Stallergènes SA, Research and Development, 6 rue Alexis de Tocqueville, 92160 Antony, France.
Van Overtvelt
Laurence
L
Lombardi
Vincent
V
Razafindratsita
Alain
A
Moussu
Hélène
H
Horiot
Stéphane
S
Chabre
Henri
H
Limal
David
D
Moutel
Stéphane
S
Bauer
Jacques
J
Chiavaroli
Carlo
C
Moingeon
Philippe
P
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000286:Administration, Sublingual; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D016764:Cell Polarity; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology; D003888:Desensitization, Immunologic / Q000379:methods*; D004151:Dipeptides / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
D000276:Adjuvants, Immunologic; D004151:Dipeptides; D007371:Interferon-gamma