Rolland-Debord Camille, Lair David, Roussey-Bihouée Tiphaine, Hassoun Dorian, Evrard Justine, Cheminant Marie-Aude, Chesné Julie, Braza Faouzi, Mahay Guillaume, Portero Vincent, Sagan Christine, Pitard Bruno, Magnan Antoine
Unité Mixte de Recherche, Institut National de la Sante et de la Recherche Médicale (U1087), Centre national de la recherche scientifique (6291), Nantes, France ; Université de Nantes, l'institut du thorax, Nantes, France.
Unité Mixte de Recherche, Institut National de la Sante et de la Recherche Médicale (U1087), Centre national de la recherche scientifique (6291), Nantes, France.
PLoS One. 2014 Jan 31;9(1):e85976. doi: 10.1371/journal.pone.0085976. eCollection 2014.
Allergic asthma is caused by abnormal immunoreactivity against allergens such as house dust mites among which Dermatophagoides farinae (Der f) is a common species. Currently, immunotherapy is based on allergen administration, which has variable effect from patient to patient and may cause serious side effects, principally the sustained risk of anaphylaxis. DNA vaccination is a promising approach by triggering a specific immune response with reduced allergenicity.
The aim of the study is to evaluate the effects of DNA immunization with Der f1 allergen specific DNA on allergic sensitization, inflammation and respiratory function in mice.
Mice were vaccinated 28 and 7 days before allergen exposure with a Der f1-encoding plasmid formulated with a block copolymer. Asthma was induced by skin sensitization followed by intra-nasal challenges with Der f extract. Total lung, broncho-alveolar lavage (BAL) and spleen cells were analyzed by flow cytometry for their surface antigen and cytokine expression. Splenocytes and lung cell IFN-γ production by CD8+ cells in response to Der f CMH1-restricted peptides was assessed by ELISPOT. IgE, IgG1 and IgG2a were measured in serum by ELISA. Specific bronchial hyperresponsiveness was assessed by direct resistance measurements.
Compared to animals vaccinated with an irrelevant plasmid, pVAX-Der f1 vaccination induced an increase of B cells in BAL, and an elevation of IL-10 and IFN-γ but also of IL-4, IL-13 and IL-17 producing CD4+ lymphocytes in lungs and of IL-4 and IL-5 in spleen. In response to CD8-restricted peptides an increase of IFN-γ was observed among lung cells. IgG2a levels non-specifically increased following block copolymer/DNA vaccination although IgE, IgG1 levels and airways resistances were not impacted.
CONCLUSIONS & CLINICAL RELEVANCE: DNA vaccination using a plasmid coding for Der f1 formulated with the block copolymer 704 induces a specific immune response in the model of asthma used herein.
过敏性哮喘是由针对过敏原（如屋尘螨，其中粉尘螨是常见种类）的异常免疫反应引起的。目前，免疫疗法基于给予过敏原，但患者之间的效果各不相同，且可能会引起严重的副作用，主要是持续存在的过敏反应风险。DNA疫苗接种是一种有前景的方法，可引发特异性免疫反应且降低过敏原性。
本研究旨在评估用粉尘螨1（Der f1）过敏原特异性DNA进行DNA免疫接种对小鼠过敏致敏、炎症和呼吸功能的影响。
在过敏原暴露前28天和7天，用与嵌段共聚物配制的编码Der f1的质粒对小鼠进行疫苗接种。通过皮肤致敏，随后用粉尘螨提取物进行鼻内激发来诱导哮喘。通过流式细胞术分析全肺、支气管肺泡灌洗（BAL）和脾细胞的表面抗原和细胞因子表达。通过ELISPOT评估脾细胞和肺细胞中CD8 +细胞对Der f CMH1限制性肽的IFN-γ产生。通过ELISA测定血清中的IgE、IgG1和IgG2a。通过直接测量阻力评估特异性支气管高反应性。
与用无关质粒接种的动物相比，pVAX-Der f1疫苗接种诱导了BAL中B细胞的增加，以及肺中产生IL-10、IFN-γ以及产生IL-4、IL-13和IL-17的CD4 +淋巴细胞和脾中IL-4和IL-5的升高。在对CD8限制性肽的反应中，肺细胞中观察到IFN-γ增加。尽管IgE、IgG1水平和气道阻力未受影响，但在嵌段共聚物/DNA疫苗接种后IgG2a水平非特异性增加。
使用与嵌段共聚物704配制的编码Der f1的质粒进行DNA疫苗接种在此处使用的哮喘模型中诱导了特异性免疫反应。
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