Factors Influencing the Allergenicity and Adjuvanticity of Allergens

Stephan Deifl; Barbara Bohle

Disclosures

Immunotherapy. 2011;3(7):881-893. 

In This Article

Allergen–flagellin Fusion Proteins

The TLR5 ligand flagellin is the main constituent of motility conferring flagella of Gram-positive and negative bacteria.[110] Flagellin has been known as adjuvant for prophylactic and therapeutic immune modulation in various diseases (e.g., virus infection).[111,112] Intranasal coadministration of flagellin with ovalbumin (OVA), a major allergen in chicken white egg, significantly suppressed OVA-induced airway hyper-responsiveness, airway eosinophilic inflammation and OVA-specific Th2-cytokine responses in OVA-sensitized mice.[113] These results indicated that flagellin can also be considered as an adjuvant for SIT. Recently, flagellin A from Listeria monocytogenes was genetically fused to OVA and tested in a murine in vitro system.[114] Compared to flagellin alone, the fusion protein induced a higher expression of maturation markers (CD40, CD69, CD80 and CD86) on myeloid DCs. Moreover, IL-6 and IL-10 production by myeloid DCs was increased when stimulated with fusion proteins in comparison to equimolar mixtures of both proteins. This observation demonstrated again that the fusion protein consisting of an allergen and a TLR ligand showed stronger immunomodulating capacity as the mixture of both components and confirmed that the approach to endow allergens with intrinsic adjuvanticity is a promising concept for the design of vaccines for future SIT. However, up to now, none of the recombinant allergen–modulator fusion proteins have been tested in clinical trials.

In addition to ligands recognized by TLR4, TLR5 and TLR9 agonists of TLR7 (e.g., imidazoquinolines or modified adenine) have been suggested as candidate adjuvants in future allergy vaccines.[115,116] These TLR7 agonists effectively redirected Th2 responses in both, in vitro and in vivo studies. However, for all of these still scientific vaccine formulations, the potential induction of adverse Th1-mediated inflammation in humans remains an issue of concern. Thus, clinical trials in humans are needed to evaluate the in vivo efficacy and potential side effects of these future allergy vaccines.

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