Allergen-specific immunotherapy of shellfish allergy: application of hypoallergen-encoding DNA vaccine

Ka Hou Chu*, Christine Y.Y. Wai, Nicki Y.H. Leung and Patrick S.C. Leung
 
School of Life Sciences, The Chinese University of Hong Kong
Shatin, N.T., Hong Kong, China
kahouchu@cuhk.edu.hk

Shellfish allergy is highly prevalent worldwide but current clinical management of shellfish allergy is limited to avoidance. Allergen-specific immunotherapy (AIT) is effective in desensitizing and/or developing tolerance in the recipients. However, conventional AIT using unmodified allergens often triggers anaphylactic side-effects. Alternative modulators with high efficacy and safety profiles are therefore urged. We have previously constructed a hypoallergen MEM49 of the major shrimp allergen tropomyosin (Met e 1). In this study, we sought to investigate the therapeutic potential of a MEM49-encoding DNA vaccine in our established mouse model of shrimp hypersensitivity.

3-4 weeks old female Balb/c mice in the positive control and MEM49-treatment groups (n = 7) were first orally sensitized and challenged with Met e 1. One week after challenge, mice in the MEM49-treatment group were intradermally treated with 100 μg pCI-neo clones of MEM49 for three times at weekly intervals. Mice in the positive control group received the same volume of PBS as shame treatment. These mice then received a second Met e 1 challenge one week after the last treatment. Mice receiving PBS throughout the experiment were included as negative controls. Blood, spleen and small intestine were then collected for antibody, cytokine, gene expression and histological analysis to evaluate the therapeutic effects of the MEM49-encoding DNA vaccine.

MEM49-encoding DNA vaccine-treated mice exhibited less severe systemic and local allergic responses, as well as significantly lower levels of Met e 1-specific IgE comparing to pre-treatment and positive controls (Table 1). Treated mice also had elevated level of specific IgG2a with inhibitory potential. In vitro splenocyte analysis also revealed significantly lower levels of IL-4 and IL-5, but higher levels of IFN-γ and IL-10 (Table 2), suggesting the ability of the DNA vaccine in suppressing Th2 allergic responses while up-regulating Th1 and regulatory T cell-associated responses. Our results therefore demonstrate that hypoallergen-based vaccine is effective in ameliorating allergic reactions to shrimp tropomyosin.

[This work was supported by the Health and Medical Research Fund (02130206), HKSAR Government.]