Comparison of intranasal and transcutaneous immunization for induction of protective immunity against Chlamydia muridarum respiratory tract infection
Comparison of intranasal and transcutaneous immunization for induction of protective immunity against Chlamydia muridarum respiratory tract infection
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DOI：
10.1016/j.vaccine.2005.07.104
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发表时间：
2006-01-16
期刊：
影响因子：
5.5
通讯作者：
Beagley, KW
中科院分区：
文献类型：
--
作者：
Skelding, KA;Hickey, DK;Beagley, KW
肺炎衣原体引起一系列呼吸道感染，包括支气管炎、咽炎和肺炎。感染还与哮喘和慢性阻塞性肺病（COPD）的恶化/引发有关，并且可能在动脉粥样硬化和阿尔茨海默病中发挥作用。我们使用衣原体呼吸道感染的小鼠模型来确定鼻内（IN）和经皮免疫（TCI）预防衣原体肺部感染的有效性。雌性 BALB/c 小鼠通过 IN 或 TO 途径用与霍乱毒素和 CpG 寡脱氧核苷酸佐剂混合的衣原体主要外膜蛋白 (MOMP) 进行免疫。收集血清和支气管肺泡灌洗液（BAL）用于抗体分析。用 MOMP 体外刺激来自肺引流淋巴结的单核细胞，并通过实时 PCR 测定细胞因子 mRNA 的产生。用活衣原体攻击动物并在攻击后每天称重。在第10天（感染高峰期）处死动物，并通过实时PCR测定肺部可恢复的衣原体数量。感染后第 10 天还测定了肺组织中 MOMP 特异性抗体分泌细胞。与未免疫对照组相比，IN 和 TO 均保护动物免于体重减轻，两个免疫组在攻击后第 10 天体重增加，而对照组体重减轻了 6%。两种免疫方案均在血清和 BAL 中诱导 MOMP 特异性 IgG，而仅 IN 免疫在 BAL 中诱导 MOMP 特异性 I-A。两种免疫途径都会在肺组织中产生大量 MOMP 特异性抗体分泌细胞 (IN > TCI)。用 MOMP 体外重新刺激肺引流淋巴结细胞后； IN 免疫动物细胞中的 IFN γ mRNA 增加了 20 倍（与未免疫对照相比），而 TO 动物中 IFN γ 水平增加了 6 至 7 倍。攻击后十天，未免疫动物的肺中具有> 7000 IFU，IN免疫动物< 50 IFU并且TO免疫动物< 1500 IFU。因此，鼻内和经皮免疫均可保护小鼠免受衣原体的呼吸道攻击。 IN 免疫后获得最佳保护，并与肺引流 LN 中单核细胞产生的 IFN γ 和 BAL 中 MOMP 特异性 IgA 相关。 (c) 2005 Elsevier Ltd. 保留所有权利。
Chlamydia pneumoniae causes a range of respiratory infections including bronchitis, pharyngitis and pneumonia. Infection has also been implicated in exacerbation/initiation of asthma and chronic obstructive pulmonary disease (COPD) and may play a role in atherosclerosis and Alzheimer's disease. We have used a mouse model of Chlamydia respiratory infection to determine the effectiveness of intranasal (IN) and transcutaneous immunization (TCI) to prevent Chlamydia lung infection. Female BALB/c mice were immunized with chlamydial major outer membrane protein (MOMP) mixed with cholera toxin and CpG oligodeoxynucleotide adjuvants by either the IN or TO routes. Serum and bronchoalveolar lavage (BAL) were collected for antibody analysis. Mononuclear cells from lung-draining lymph nodes were stimulated in vitro with MOMP and cytokine mRNA production determined by real time PCR. Animals were challenged with live Chlamydia and weighed daily following challenge. At day 10 (the peak of infection) animals were sacrificed and the numbers of recoverable Chlamydia in lungs determined by real time PCR. MOMP-specific antibody-secreting cells in lung tissues were also determined at day 10 post-infection. Both IN and TO protected animals against weight loss compared to non-immunized controls with both immunized groups gaining weight by day 10-post challenge while controls had lost 6% of body weight. Both immunization protocols induced MOMP-specific IgG in serum and BAL while only IN immunization induced MOMP-specific I-A in BAL. Both immunization routes resulted in high numbers of MOMP-specific antibody-secreting cells in lung tissues (IN > TCI). Following in vitro re-stimulation of lung-draining lymph node cells with MOMP; IFN gamma mRNA increased 20-fold in cells from IN immunized animals (compared to non-immunized controls) while IFN gamma levels increased 6- to 7-fold in TO animals. Ten days post challenge non-immunized animals had > 7000 IFU in their lungs, IN immunized animals < 50 IFU and TO immunized animals < 1500 IFU. Thus, both intranasal and transcutaneous immunization protected mice against respiratory challenge with Chlamydia. The best protection was obtained following IN immunization and correlated with IFN gamma production by mononuclear cells in lung-draining LN and MOMP-specific IgA in BAL. (c) 2005 Elsevier Ltd. All rights reserved.