A Fusion Protein of Derp2 Allergen and Flagellin Suppresses Experimental Allergic Asthma
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Published on: June 4, 2017
Wenzhi Tan1, Jin Hai Zheng2, Tra My Nu Duong1
1Clinical Vaccine R&D Center and Department of Microbiology, Chonnam National University Medical School, Gwangju, Korea.
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.
Insights
A novel Derp2-FlaB fusion protein effectively treats house dust mite (HDM) induced asthma in mice. This fusion protein significantly reduces airway inflammation and hyperresponsiveness, offering a promising therapeutic vaccine candidate for allergic asthma.
Area of Science:
- Immunology
- Allergology
- Biotechnology
Background:
- House dust mite (HDM) allergens are major triggers for allergic rhinitis and asthma.
- Previous research showed *Vibrio vulnificus* flagellin B (FlaB) combined with allergens can improve lung function and reduce airway inflammation via Toll-like receptor 5 signaling.
- This study investigates a new therapeutic approach by fusing a key HDM allergen, Derp2, with FlaB.
Purpose of the Study:
- To compare the therapeutic efficacy of a Derp2-FlaB fusion protein against a mixture of Derp2 and FlaB.
- To evaluate the anti-asthma immunomodulatory capacity of the Derp2-FlaB fusion protein in a Derp2-induced mouse asthma model.
Main Methods:
- BALB/c mice were sensitized with Derp2 and HDM.
- Mice received treatments of Derp2 alone, a Derp2 + FlaB mixture, or the Derp2-FlaB fusion protein.
- Airway responses and immune responses were assessed after intranasal challenge with Derp2.
Main Results:
- The Derp2-FlaB fusion protein demonstrated superior efficacy compared to the Derp2 + FlaB mixture.
- Significant reductions were observed in airway hyperresponsiveness, lung eosinophil infiltration, and Derp2-specific IgE levels with the fusion protein.
- The fusion protein effectively inhibited Th2 responses, indicating strong anti-asthma immunomodulatory effects.
Conclusions:
- The Derp2-FlaB fusion protein exhibits significant anti-asthma properties by preventing airway inflammation in a murine model.
- This fusion protein shows promise as a vaccine candidate for therapeutic intervention in HDM-mediated allergic asthma.
- Targeting Th2 responses is a key mechanism for the observed therapeutic benefits.
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