BACKGROUND: Although there have been many therapeutic options for allergic disease, the true allergen desensitization remains a challenging goal. The classic immunotherapy has a limited efficacy, is inconvenient, and has a risk of anaphylaxis. Recent reports revealed that immunostimulatory DNA sequences (ISS-oligdeoxynucleotide [ODN], CpG motif) act as a strong Th1 response-inducing adjuvants and that DNA-based vaccination might be an effective therapeutic option. In this study, we investigate whether ISS-ODN/Dermatophagoides farinae (Der f) conjugate has antiallergic effects in the allergic rhinitis mouse model, sensitive to house-dust mites. Der f is the most common allergen-inducing allergic rhinitis in Korea. METHODS: C57BL/6 mice were sensitized with crude extract of Der f. After injection of ISS-ODN or ISS-ODN/Der f conjugate, several parameters of allergic response were evaluated. RESULTS: Scratching and sneezing symptoms and eosinophilic infiltration into nasal mucosa were suppressed by injection with ISS-ODN only and ISS-ODN/Der f conjugate. Interleukin-5 level was decreased and interferon gamma level was increased in nasal lavage fluid by injection of ISS-ODN/Der f conjugate. Der f-specific immunoglobulin E was decreased by injection of ISS-ODN or Der f /ISS-ODN conjugate; however, these were not statistically significant. Transforming growth factor beta1 secreted by cultured splenocyte was increased significantly in ISS-ODN/Der f conjugate group. CONCLUSION: These results suggest ISS-ODN/Der f conjugate induces an antiallergic effect and induces an increase in transforming growth factor beta1 level in the allergic rhinitis model using Der f allergen. Allergic response developed by Der f allergen could be more effectively reduced by injection with ISS-ODN/Der f conjugate than by injection with ISS-ODN only.
BACKGROUND: Although there have been many therapeutic options for allergic disease, the true allergen desensitization remains a challenging goal. The classic immunotherapy has a limited efficacy, is inconvenient, and has a risk of anaphylaxis. Recent reports revealed that immunostimulatory DNA sequences (ISS-oligdeoxynucleotide [ODN], CpG motif) act as a strong Th1 response-inducing adjuvants and that DNA-based vaccination might be an effective therapeutic option. In this study, we investigate whether ISS-ODN/Dermatophagoides farinae (Der f) conjugate has antiallergic effects in the allergic rhinitismouse model, sensitive to house-dust mites. Der f is the most common allergen-inducing allergic rhinitis in Korea. METHODS: C57BL/6 mice were sensitized with crude extract of Der f. After injection of ISS-ODN or ISS-ODN/Der f conjugate, several parameters of allergic response were evaluated. RESULTS: Scratching and sneezing symptoms and eosinophilic infiltration into nasal mucosa were suppressed by injection with ISS-ODN only and ISS-ODN/Der f conjugate. Interleukin-5 level was decreased and interferon gamma level was increased in nasal lavage fluid by injection of ISS-ODN/Der f conjugate. Der f-specific immunoglobulin E was decreased by injection of ISS-ODN or Der f /ISS-ODN conjugate; however, these were not statistically significant. Transforming growth factor beta1 secreted by cultured splenocyte was increased significantly in ISS-ODN/Der f conjugate group. CONCLUSION: These results suggest ISS-ODN/Der f conjugate induces an antiallergic effect and induces an increase in transforming growth factor beta1 level in the allergic rhinitis model using Der f allergen. Allergic response developed by Der f allergen could be more effectively reduced by injection with ISS-ODN/Der f conjugate than by injection with ISS-ODN only.
Authors: Vijaya B Joshi; Andrea Adamcakova-Dodd; Xuefang Jing; Amaraporn Wongrakpanich; Katherine N Gibson-Corley; Peter S Thorne; Aliasger K Salem Journal: AAPS J Date: 2014-07-01 Impact factor: 4.009
Authors: Emil F Khisamutdinov; Hui Li; Daniel L Jasinski; Jiao Chen; Jian Fu; Peixuan Guo Journal: Nucleic Acids Res Date: 2014-08-04 Impact factor: 16.971