Mucosal immunization with Shigella flexneri outer membrane vesicles induced protection in mice
Mucosal immunization with Shigella flexneri outer membrane vesicles induced protection in mice
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DOI：
10.1016/j.vaccine.2011.08.121
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发表时间：
2011-10-26
期刊：
影响因子：
5.5
通讯作者：
Gamazo, C.
中科院分区：
文献类型：
--
作者：
Camacho, A. I.;de Souza, J.;Gamazo, C.
疫苗接种似乎是控制志贺氏菌病的唯一合理的预防方法。不幸的是，仍然没有安全有效的疫苗。我们在小鼠志贺氏菌病实验模型中研究了一种含有福氏志贺氏菌外膜囊泡 (OMV) 和基于纳米粒子的佐剂的新疫苗所提供的保护作用。 OMVs被封装在通过溶剂置换法用共聚物PMV/MA制备的聚酸酐纳米颗粒中。装载到 NP 中的 OMV (NP-OMV) 形状均匀，呈球形，尺寸为 197 nm (PdI = 0.06)。 BALB/c小鼠（雌性，9周龄，20+/-1g）通过皮内、鼻腔、眼部（20μg）或口服途径（100μg）用游离或胶囊化的OMV进行免疫。给药后 35 天，小鼠鼻内感染致死剂量的福氏链球菌 (1 x 10(7) CFU)。当通过粘膜注射时，新疫苗能够充分防止感染。通过皮内途径，NP-OMV 配方将保护作用从游离提取物的 20% 提高到 100%。有趣的是，通过鼻腔和结膜途径给药时，OMV 和 OMV-NP 均能产生全面的保护作用。发现 IL-12p40/IL-10 的比率与保护作用之间存在很强的相关性。此外，低水平的 IFN-γ 与保护作用相关。在所使用的实验条件下，佐剂没有引起任何不良反应。这些结果使 OMV 成为用于志贺氏菌病疫苗接种的有希望的候选者之一。 (C) 2011 Elsevier Ltd. 保留所有权利。
Vaccination appears to be the only rational prophylactic approach to control shigellosis. Unfortunately, there is still no safe and efficacious vaccine available. We investigated the protection conferred by a new vaccine containing outer membrane vesicles (OMVs) from Shigella flexneri with an adjuvant based on nanoparticles in an experimental model of shigellosis in mice. OMVs were encapsulated in poly(anhydride) nanoparticles prepared by a solvent displacement method with the copolymer PMV/MA. OMVs loaded into NPs (NP-OMVs) were homogeneous and spherical in shape, with a size of 197 nm (PdI = 0.06). BALB/c mice (females, 9-week-old, 20 +/- 1 g) were immunized by intradermal, nasal, ocular (20 mu g) or oral route (100 mu g) with free or encapsulated OMV. Thirty-five days after administration, mice were infected intranasally with a lethal dose of S. flexneri (1 x 10(7) CFU). The new vaccine was able to protect fully against infection when it was administered via mucosa. By intradermal route the NP-OMVs formulation increased the protection from 20%, obtained with free extract, to 100%. Interestingly, both OMVs and OMV-NP induced full protection when administered by the nasal and conjuntival route. A strong association between the ratio of IL-12p40/IL-10 and protection was found. Moreover, low levels of IFN-gamma correlate with protection. Under the experimental conditions used, the adjuvant did not induce any adverse effects. These results place OMVs among promising candidates to be used for vaccination against Shigellosis. (C) 2011 Elsevier Ltd. All rights reserved.