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荆豆凝集素I修饰脂质体用于口服疫苗:体外生物黏附及体内免疫

Application of Ulex europaeus agglutinin I-modified liposomes for oral vaccine: Ex Vivo bioadhesion and in Vivo immunity.

作者信息

Li KeXin, Zhao Xiuli, Xu Shiyi, Pang DaHai, Yang ChunRong, Chen DaWei

机构信息

School of Pharmacy, Shenyang Pharmaceutical University, Liaoning, China.

出版信息

Chem Pharm Bull (Tokyo). 2011;59(5):618-23. doi: 10.1248/cpb.59.618.

Abstract

The conjugation of Ulex europaeus agglutinin I (UEAI) onto surface of liposomes has been demonstrated to effectively improve the intestinal absorption of antigen, subsequently induced strong mucosal and systemic immune responses. In this context, we prepared bovine serum albumin (BSA)-encapsulating UEAI-modified liposomes (UEAI-LIP) and unmodified ones (LIP). The specific bioadhesion on mice gastro-intestinal mucosa was studied ex vivo. An important increase of interaction between UEAI-conjugated liposomes and the intestinal segments with Peyer's Patches (PPs) was observed compared with the unconjugated one (p<0.01). However, under the presence of α-L-fucose, which is the reported specific sugar for UEAI, specifically inhibited the activity of these conjugates. The immune-stimulating activity in vivo was studied by measuring immunoglobulin G (IgG) levels in serum and immunoglobulin A (IgA) levels in intestinal mucosal secretions following oral administration of BSA solution, LIP and UEAI-LIP in mice. Results indicate that antigen encapsulated in liposomes, especially the UEAI-modified ones, was favorable for inducing immune response. At 42 d after the first immunization, the highest IgG and IgA antibody levels produced by UEAI-LIP occurred, respectively showing 4.4-fold and 5-fold higher levels compared to those of the groups receiving BSA alone. This data demonstrated high potential of UEAI-modified liposomes for their use as carrier for oral vaccines.

摘要

已证明将欧洲荆豆凝集素I(UEAI)偶联到脂质体表面可有效改善抗原的肠道吸收,随后诱导强烈的黏膜和全身免疫反应。在此背景下,我们制备了包封牛血清白蛋白(BSA)的UEAI修饰脂质体(UEAI-LIP)和未修饰的脂质体(LIP)。对小鼠胃肠道黏膜的特异性生物黏附进行了体外研究。与未偶联的脂质体相比,观察到UEAI偶联的脂质体与含有派尔集合淋巴结(PPs)的肠段之间的相互作用显著增加(p<0.01)。然而,在存在α-L-岩藻糖(据报道是UEAI的特异性糖)的情况下,它特异性地抑制了这些偶联物的活性。通过测量小鼠口服BSA溶液、LIP和UEAI-LIP后血清中的免疫球蛋白G(IgG)水平和肠道黏膜分泌物中的免疫球蛋白A(IgA)水平,研究了体内免疫刺激活性。结果表明,包裹在脂质体中的抗原,尤其是UEAI修饰的脂质体,有利于诱导免疫反应。首次免疫后42天,UEAI-LIP产生的IgG和IgA抗体水平最高,分别比单独接受BSA的组高出4.4倍和5倍。该数据表明UEAI修饰的脂质体作为口服疫苗载体具有很高的潜力。

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