Wang Yuqian, Sha Jichao, Wang Heng, An Lifeng, Liu Tie, Li Lin
Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China.
Department of Otorhinolaryngology Head and Neck Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China.
Mol Ther Methods Clin Dev. 2018 Oct 4;11:83-91. doi: 10.1016/j.omtm.2018.09.004. eCollection 2018 Dec 14.
Allergic rhinitis (AR) involves antigen-specific immune-inflammation of the nasal mucosa. Classical therapy for AR targets the histamine pathway, e.g., histamine receptor blockers. Histamine H4 receptor (H4R) was suggested as a novel therapeutic target due to its wide expression on almost all immune-related cells. A 12-mer random peptide library was used to select the specific epitope of the H4R. The phage clone showing the highest degree of activation was verified and translated to the corresponding peptide. The peptide FNKWMDCLSVTH, designated as P-FN12, was bound by H4R monoclonal antibody (mcAb) with high affinity. Moreover, the P-FN12 + CTB@Lipo-formulated vaccine, used as nasal drops, decreased allergic symptoms such as sneezing and nasal rubbing in a rat model. The level of ovalbumin (OVA)-specific immunoglobulin E (IgE) decreased significantly after vaccine administration. It also elicited increased levels of interferon (IFN)-γ and interleukin-2 (IL-2) but a decreased level of IL-4, and it elevated the T helper type 1 (Th1):T helper type 2 (Th2) cell ratio in peripheral blood mononuclear cell cultures. Our results indicated that the reduction of allergic inflammation by P-FN12-based vaccine was related to a decrease in production of OVA-specific IgE, Th2 immunity, and tissue eosinophilia. P-FN12 + CTB@Lipo is a promising vaccine that could suppress Th2 response and enhance the induction of Th1 cells in an AR model.
变应性鼻炎（AR）涉及鼻黏膜的抗原特异性免疫炎症。AR的传统治疗针对组胺途径，例如组胺受体阻滞剂。组胺H4受体（H4R）因其在几乎所有免疫相关细胞上广泛表达而被认为是一种新的治疗靶点。利用一个12肽随机肽库筛选H4R的特异性表位。对显示出最高激活程度的噬菌体克隆进行验证，并将其翻译为相应的肽。命名为P-FN12的肽FNKWMDCLSVTH与H4R单克隆抗体（mcAb）具有高亲和力结合。此外，制成滴鼻剂的P-FN12 + CTB@脂质体疫苗可减轻大鼠模型中的打喷嚏和蹭鼻等变应性症状。疫苗接种后，卵清蛋白（OVA）特异性免疫球蛋白E（IgE）水平显著降低。它还使干扰素（IFN）-γ和白细胞介素-2（IL-2）水平升高，但使IL-4水平降低，并提高了外周血单个核细胞培养物中1型辅助性T细胞（Th1）与2型辅助性T细胞（Th2）的比例。我们的结果表明，基于P-FN12的疫苗减轻变应性炎症与OVA特异性IgE产生减少、Th2免疫反应及组织嗜酸性粒细胞增多的降低有关。P-FN12 + CTB@脂质体是一种有前景的疫苗，可在AR模型中抑制Th2反应并增强Th1细胞的诱导。
