Ovalbumin fused with diphtheria toxin protects mice from ovalbumin inducedanaphylactic shock

For those with allergy, vaccination with a specific allergen has often been used as a major therapeutic measure. However, the universal application of this technique in clinics have been restricted due to its low success rate s and the risk of active systemic anaphylactic shock (ASAS). In this regard , we constructed a fusion protein (OVA-DT), ovalbumin (OVA) fused with diph theria toxin protein (DT), which may exert a specific cytotoxicity to cells bearing OVA-specific IgE. Its therapeutic effect was evaluated in mice (BA LB/c) sensitized with OVA (Os-mice). OVA challenges to the OVA-sensitized m ice (Os-mice) caused ASAS to death within 30 min, but OVA-DT treatment affo rded mice complete protection. When OVA-DT was treated to the Os-mice, none showed the signs of ASAS when re-challenged 48 h after the treatment. OVA- DT itself was not found to be toxic or allergenic in normal mice. The effec t of OVA-DT on the biological functions of mast cells was also studied. Bin ding of OVA-DT to OVA-specific IgE bearing mast cells and the inhibition of histamine release from these cells were observed. In addition, OVA-DT trea tment inhibited the proliferation of OVA-specific B cells in mice. In Os-mi ce treated with OVA-DT, levels of anti-OVA IgG2a in serum and the productio n of IFN-gamma by splenic lymphocytes were found to increase, but the produ ction of IL-4 by these cells decreased. Re-direction of cytokine profiles f rom OVA-specific Th2 to OVA-specific Th1 is suggested. These results indicate that OVA-DT can protect Os-mice from ASAS due to OVA challenge, because it inactivates OVA-specific IgE-expressing cells, inclu ding mast cells and B cells.