期刊
ALLERGY ASTHMA & IMMUNOLOGY RESEARCH
卷 11, 期 2, 页码 254-266出版社
KOREAN ACAD ASTHMA ALLERGY & CLINICAL IMMUNOLOGY
DOI: 10.4168/aair.2019.11.2.254
关键词
Asthma; Derp2; FlaB flagellin; fusion protein; Toll-like receptor 5
资金
- Korea Health Technology R&D Project - Ministry of Health & Welfare, Republic of Korea [HI14C0187]
- National Program for Cancer Control, Ministry of Health & Welfare of the Republic of Korea [HA17C0038 [1720120]]
- Bio & Medical Technology Development Program of the National Research Foundation of Korea (NRF) - Korean government, Ministry of Science, ICT and Future Planning (MSIP) [NRF-2017M3A9E2056372]
Purpose: The house dust mite (HDM) is one of the most important sources of indoor allergens and a significant cause of allergic rhinitis and allergic asthma. Our previous studies demonstrated that Vibrio vulnificus flagellin B (FlaB) plus allergen as a co-treatment mixture improved lung function and inhibited eosinophilic airway inflammation through the Toll-like receptor 5 signaling pathway in an ovalbumin (OVA)- or HDM-induced mouse asthma model. In the present study, we fused the major mite allergen Derp2 to FlaB and compared the therapeutic effects of the Derp2-FlaB fusion protein with those of a mixture of Derp2 and FlaB in a Derp2-induced mouse asthma model. Methods: BALB/c mice sensitized with Derp2 + HDM were treated with Derp2, a Derp2 plus FlaB (Derp2 + FlaB) mixture, or the Derp2-FlaB fusion protein 3 times at 1-week intervals. Seven days after the final treatment, the mice were challenged intranasally with Derp2, and airway responses and Derp2-specific immune responses were evaluated. Results: The Derp2-FlaB fusion protein was significantly more efficacious in reducing airway hyperresponsiveness, lung eosinophil infiltration, and Derp2-specific IgE than the Derp2 + FlaB mixture. Conclusions: The Derp2-FlaB fusion protein showed a strong anti-asthma immunomodulatory capacity, leading to the prevention of airway inflammatory responses in a murine disease model through the inhibition of Th2 responses. These findings suggest that the Derp2-FlaB fusion protein would be a promising vaccine candidate for HDM-mediated allergic asthma therapy.
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