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首页> 外文期刊>Allergy >A recombinant allergen chimer as novel mucosal vaccine candidate for prevention of multi-sensitivities.
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A recombinant allergen chimer as novel mucosal vaccine candidate for prevention of multi-sensitivities.

机译：重组变应原嵌合体作为预防多种敏感性的新型粘膜疫苗候选者。

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BACKGROUND: As conventional immunotherapy is less efficacious in patients with allergic multi-sensitivities compared with mono-sensitized subjects, new intervention strategies are needed. Therefore, an allergen chimer was genetically engineered for treatment of multi-sensitization with birch and grass pollen on the basis of mucosal tolerance induction. METHODS: The major birch pollen allergen Bet v 1 served as a scaffold for N- and C-terminal linkage of the immunodominant peptides of the grass pollen allergens Phl p 1 and Phl p 5 and this new construct was cloned and expressed in Escherichia coli. After purification, physicochemical and immunological characterization the chimer was used for intranasal tolerance induction prior to poly-sensitization with Bet v 1, Phl p 1 and Phl p 5. RESULTS: The immunological characterization revealed that the conformation of Bet v 1 within the chimer was comparable to that of natural as well as recombinant Bet v 1. The chimer was immunogenic in mice for T and B cell responses to the three allergens. Intranasal application of the chimer prior to poly-sensitization significantly suppressed humoral and cellular allergen-specific Th2 responses and prevented development of airway inflammation upon allergen challenge. Moreover, local allergen-specific IgA antibodies were induced by the chimer. The mechanisms of poly-tolerance induction seemed to be mediated by regulatory cytokines, since TGF-beta and IL-10 mRNA in splenocytes were upregulated and tolerance was transferable with these cells. CONCLUSION: The data indicate that such allergen chimers harboring several unrelated allergens or allergen peptides could serve as mucosal polyvalent vaccines for prevention of multi-sensitivities.
机译：背景：由于传统的免疫疗法对过敏性多敏性患者的疗效不如单敏性受试者，因此需要新的干预策略。因此，在粘膜耐受性诱导的基础上，对一种过敏原嵌合基因进行了基因工程改造，以治疗桦木和花粉的多重致敏作用。方法：主要桦树花粉变应原Bet v 1充当草花粉变应原Phl p 1和Phl p 5的免疫显性肽的N端和C端连接的支架，并在大肠杆菌中克隆并表达该新构建体。纯化，理化和免疫学表征后，将嵌合体用于鼻内耐受诱导，然后与Bet v 1，Phl p 1和Phl p 5进行多敏化。结果：免疫学表征表明，该嵌合体中Bet v 1的构象为与天然和重组Bet v 1相当。该嵌合体在小鼠中对三种过敏原的T细胞和B细胞反应均具有免疫原性。在多敏化之前在鼻内应用嵌合体可显着抑制体液和细胞过敏原特异性Th2反应，并防止在过敏原激发后气道炎症的发展。此外，嵌合体诱导了局部变应原特异性的IgA抗体。多耐受诱导的机制似乎是由调节性细胞因子介导的，因为脾细胞中的TGF-β和IL-10 mRNA上调且耐受性可通过这些细胞转移。结论：数据表明，这种具有几种不相关的过敏原或过敏原肽的过敏原嵌合体可作为粘膜多价疫苗，以预防多重敏感性。

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