P-FN12, an H4R-Based Epitope Vaccine Screened by Phage Display, Regulates the Th1/Th2 Balance in Rat Allergic Rhinitis.
P-FN12, an H4R-Based Epitope Vaccine Screened by Phage Display, Regulates the Th1/Th2 Balance in Rat Allergic Rhinitis.
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P-FN12，一种基于 H4R 的表位疫苗，通过噬菌体展示筛选，调节大鼠过敏性鼻炎的 Th1/Th2 平衡
DOI：
10.1016/j.omtm.2018.09.004
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发表时间：
2018-12-14
期刊：
影响因子：
--
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Wang Y;Sha J;Wang H;An L;Liu T;Li L
变应性鼻炎（AR）涉及鼻粘膜的抗原特异性免疫炎症。AR的经典疗法靶向组胺途径，例如，组胺受体阻滞剂。组胺H4受体（Histamine H4 receptor，H4 R）广泛表达于几乎所有的免疫相关细胞，被认为是一个新的治疗靶点。用12肽随机肽库筛选H4 R的特异性表位。验证显示最高活化程度的噬菌体克隆并将其翻译成相应的肽。肽FNKWMDCLSVth（命名为P-FN 12）与H4 R单克隆抗体（McAb）以高亲和力结合。此外，作为滴鼻剂使用的P-FN 12 + CTB@ Lipo配制的疫苗在大鼠模型中减少了过敏症状，如打喷嚏和擦鼻。卵清蛋白（OVA）特异性免疫球蛋白E（IgE）水平在疫苗接种后显著降低。它还引起干扰素（IFN）-γ和白细胞介素-2（IL-2）水平升高，但IL-4水平降低，并提高外周血单核细胞培养物中辅助性T细胞1型（Th 1）：辅助性T细胞2型（Th 2）细胞的比例。我们的研究结果表明，P-FN 12为基础的疫苗过敏性炎症的减少与OVA特异性IgE，Th 2免疫和组织嗜酸性粒细胞增多症的产生减少有关。P-FN 12 + CTB@Lipo是一种有前途的疫苗，可以抑制AR模型中的Th 2应答并增强Th 1细胞的诱导。
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.
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影响因子：
3.7
作者：
Martinel Lamas DJ;Carabajal E;Prestifilippo JP;Rossi L;Elverdin JC;Merani S;Bergoc RM;Rivera ES;Medina VA
通讯作者：
Medina VA
影响因子：
2.8
作者：
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通讯作者：
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影响因子：
5.4
作者：
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影响因子：
3.7
作者：
Tasaniyananda N;Chaisri U;Tungtrongchitr A;Chaicumpa W;Sookrung N
通讯作者：
Sookrung N
影响因子：
12.4
作者：
Rossbach, K.;Schaper, K.;Baeumer, W.
通讯作者：
Baeumer, W.