Supression of allergic reactions by transdermal administration of allergens conjugated to cholera toxin or fragments thereof

摘要

The present invention discloses the use of the non-toxic cell-binding B subunit of CT (CTB), and holotoxin CT that is devoid of ADP-ribosylating activity, as adjuvants for enhancing transcutaneous immune response to a co-administered protein allergen. It was found that topical administration of CTB to mice induced serum antibody response against itself comparable to those evoked by CT, but was inefficient at promoting systemic antibody responses against an admixed prototype protein allergen. To the contrary co-administration of either CT or CTB with allergen led to vigorous antigen-specific T cell proliferative responses in lymph nodes draining the cutaneous site of administration and at distant systemic sites. Consistent with these observations, it was found that CTB selectively potentiated Th1-driven responses without affecting Th2-dependent responses. Cutaneously applied CT enhanced serum IgE responses to a co-administered allergen, while CTB partially suppressed epicutaneously induced IgE responses to the same allergen.