Monophosphoryl lipid A enhances nontypeable Haemophilus influenzae-specific mucosal and systemic immune responses by intranasal immunization
Monophosphoryl lipid A enhances nontypeable Haemophilus influenzae-specific mucosal and systemic immune responses by intranasal immunization
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DOI：
10.1016/j.ijporl.2017.03.018
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发表时间：
2017-06-01
影响因子：
1.5
通讯作者：
Suzuki, Masashi
中科院分区：
文献类型：
--
作者：
Iwasaki, Taro;Hirano, Takashi;Suzuki, Masashi
目的：急性中耳炎（AOM）是儿童最常见的感染性疾病之一。非分型流感嗜血杆菌（NTHi）是革兰氏阴性菌，被认为是AOM和呼吸道感染的主要病原体。在这项研究中，我们使用单磷酰脂质A（MPL），一种Toll样受体（TLR）4激动剂，作为佐剂来诱导针对NTHi的粘膜免疫应答以增强从鼻咽的细菌清除。对照小鼠仅给予磷酸盐缓冲盐水。免疫后，用NTHi攻击这些小鼠。在细菌攻击后6和12 h，处死小鼠，收集鼻洗液和血清。NTHi-和OMP-特异性抗体的数量进行了定量通过酶联免疫吸附试验。结果：MPL 10和20 μ g组产生了显着减少细菌的数量从鼻咽部回收12小时后，细菌的挑战相比，对照组。OMP特异性伊加滴度也增加MPL组相比，对照组和OMP groups.Conclusion：MPL是适合于引发有效的粘膜免疫反应，对NTHi在鼻咽。这些结果证明了佐剂的可能性，所述佐剂涉及通过TLR 4激动剂如MPL刺激先天免疫系统用于粘膜接种。(C)2017爱思唯尔B. V.保留所有权利。
Objective: Acute otitis media (AOM) is one of the most common infectious diseases in children. Non typeable Haemophilus influenzae (NTHi) is Gram-negative bacteria that are considered major pathogens of AOM and respiratory tract infections. In this study, we used monophosphoryl lipid A (MPL), a toll -like receptor (TLR) 4 agonist, as an adjuvant to induce mucosal immune responses against NTHi to enhance bacterial clearance from the nasopharynx.Methods: Mice were administered 10 jig outer membrane protein (OMP) from NTHi and 0, 10, or 20 mu g MPL intranasally once a week for 3 weeks. Control mice were administered phosphate-buffered saline alone. After immunization, these mice were challenged with NTHi. At 6 and 12 h after bacterial challenge, the mice were killed and nasal washes and sera were collected. The numbers of NTHi- and OMP-specific antibodies were quantified by enzyme-linked immunosorbent assay.Results: The MPL 10 and 20 mu g group produced a significant reduction in the number of bacteria recovered from the nasopharynx at 12 h after bacterial challenge compared to the control group. OMP-specific IgA titers were also augmented in the MPL groups compared to the control and OMP groups.Conclusion: MPL is suitable for eliciting effective mucosal immune responses against NTHi in the nasopharynx. These results demonstrate the possibility of an adjuvant that involves stimulation of the innate immune system by TLR4 agonists such as MPL for mucosal vaccination. (C) 2017 Elsevier B.V. All rights reserved.