A Combination Vaccine for Allergy and Rhinovirus Infections Based on Rhinovirus-Derived Surface Protein VP1 and a Nonallergenic Peptide of the Major Timothy Grass Pollen Allergen Phl p 1
A Combination Vaccine for Allergy and Rhinovirus Infections Based on Rhinovirus-Derived Surface Protein VP1 and a Nonallergenic Peptide of the Major Timothy Grass Pollen Allergen Phl p 1
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DOI：
10.4049/jimmunol.0713622
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发表时间：
2009-05-15
影响因子：
4.4
通讯作者：
Valenta, Rudolf
中科院分区：
文献类型：
--
作者：
Edlmayr, Johanna;Niespodziana, Katarzyna;Valenta, Rudolf
过敏原和鼻病毒感染是呼吸道疾病最常见的诱发因素。我们报告了一种重组组合疫苗的过敏和鼻病毒感染的鼻病毒衍生的VP 1，表面蛋白，这是至关重要的参与呼吸道细胞的感染，和一个非过敏性肽的主要草花粉过敏原Phi P 1的基础上的建设。在大肠杆菌中表达了由VP 1和31个氨基酸的Phip 1衍生肽组成的重组杂合分子。杂交分子不与草花粉过敏患者的IgE抗体反应，并且当暴露于过敏患者的嗜碱性粒细胞时缺乏过敏活性。在免疫小鼠和兔后，杂交体不对Phi p I致敏，但诱导保护性IgG Ab，其与来自不同草类的第1组变应原交叉反应，并阻断过敏患者对Phi p 1的IgE反应性以及Phi p 1诱导的嗜碱性粒细胞脱粒。此外，混合诱导的IgG抗体抑制鼻病毒感染培养的人上皮细胞。将非变应原性变应原衍生肽融合到病毒载体蛋白上的原理可用于工程化也保护免受病毒感染的安全过敏疫苗。免疫学杂志，2009，182：6298-6306.
Allergens and rhinovirus infections are among the most common elicitors of respiratory diseases. We report the construction of a recombinant combination vaccine for allergy and rhinovirus infections based on rhinovirus-derived VP1, the surface protein which is critically involved in infection of respiratory cells, and a nonallergenic peptide of the major grass pollen allergen Phi p 1. Recombinant hybrid molecules consisting of VP1 and a Phi p 1-derived peptide of 31 aa were expressed in Escherichia coli. The hybrid molecules did not react with IgE Abs from grass pollen allergic patients and lacked allergenic activity when exposed to basophils from allergic patients. Upon immunization of mice and rabbits, the hybrids did not sensitize against Phi p I but induced protective IgG Abs that cross-reacted with group 1 allergens from different grass species and blocked allergic patients' IgE reactivity to Phi p 1 as well as Phi p 1-induced basophil degranulation. Moreover, hybrid-induced IgG Abs inhibited rhinovirus infection of cultured human epithelial cells. The principle of fusing nonallergenic allergen-derived peptides onto viral carrier proteins may be used for the engineering of safe allergy vaccines which also protect against viral infections. The Journal of Immunology, 2009, 182: 6298-6306.