Toll-like receptor ligands as adjuvants in allergen-specific immunotherapy.
BACKGROUND
Allergen-specific immunotherapy (SIT) leads to long-term amelioration of T-helper type 2 (Th2)-mediated allergic symptoms and is therefore recommended as a first line therapy for allergies. The major disadvantage of SIT is its low efficiency, requiring treatment over years.


OBJECTIVE
In this study, we evaluated the potential of Toll-like receptor (TLR) ligands to facilitate Th1-type immune responses.


METHODS
The immunogenicity and therapeutic potential of the major bee venom allergen phospholipase A2 (PLA2) combined with various TLR ligands were tested in mice and compared with immune responses induced by conventional aluminium-based preparations.


RESULTS
Regarding total IgG against PLA2, TLR2/4-binding lipopolysaccharide and TLR3-binding polyriboinosinic polyribocytidylic (PolyI:C) were the superior adjuvants for prophylactic vaccination. However, TLR9-binding phosphorothioate-modified cytosine-guanosine-rich oligonucleotide (CpG), TLR-3-binding PolyI:C, and TLR2/6-binding peptidoglycan skewed the immune responses more towards IgG2a isotype and Th1 cytokines. Furthermore, in a therapeutic approach, CpG, PolyI:C and TLR7/8-binding 3M003 had immune modulating properties as they suppressed established IgE titres.


CONCLUSIONS
The potential of TLR ligands to adjuvate the immunogenicity of bee venom PLA2 and to skew the Th1-Th2 balance proved very heterogeneous. With respect to SIT, CpG, PolyI:C, and 3M003 were very promising. Hence, TLR ligands should be considered as adjuvants or immune modulators in SIT in human as to improve its efficiency regarding the Th1-Th2 balance of the immune response with a likely effect on therapy duration.
Johansen
P
P
Unit for Experimental Immunotherapy, University Hospital of Zurich, Zurich, Switzerland. pal.johansen@usz.ch
Senti
G
G
Martinez Gomez
J M
JM
Storni
T
T
von Beust
B R
BR
Wüthrich
B
B
Bot
A
A
Kündig
T M
TM
D000276:Adjuvants, Immunologic; D000485:Allergens / Q000276:immunology / Q000627:therapeutic use*; D000818:Animals; D000906:Antibodies / Q000097:blood; D000937:Antigen-Antibody Reactions; D016207:Cytokines / Q000097:blood; D003888:Desensitization, Immunologic / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008808:Mice, Inbred CBA; D023421:Models, Animal; D010741:Phospholipases A / Q000276:immunology / Q000627:therapeutic use; D054467:Phospholipases A2; D018417:Th1 Cells / Q000276:immunology*; D051193:Toll-Like Receptors / Q000378:metabolism*; D014611:Vaccination
D000276:Adjuvants, Immunologic; D000485:Allergens; D000906:Antibodies; D016207:Cytokines; D008024:Ligands; D051193:Toll-Like Receptors; D010741:Phospholipases A; D054467:Phospholipases A2