Outer membrane vesicles obtained from Bordetella pertussis Tohama expressing the lipid A deacylase PagL as a novel acellular vaccine candidate
Outer membrane vesicles obtained from Bordetella pertussis Tohama expressing the lipid A deacylase PagL as a novel acellular vaccine candidate
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DOI：
10.1016/j.vaccine.2010.12.068
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发表时间：
2011-02-11
期刊：
影响因子：
5.5
通讯作者：
Hozbor, Daniela
中科院分区：
文献类型：
--
作者：
Asensio, Cristian J. A.;Emilia Gaillard, Maria;Hozbor, Daniela
为了设计一种更安全有效的无菌百日咳疫苗，设计了外膜囊泡(OMV)来降低其内毒素。在百日咳杆菌Tohama-I中表达了编码类脂A3-脱酰基酶的PagL基因，该OMVSBpPagL除了含有百日咳表面免疫原百日咳蛋白和百日咳毒素外，还含有四酰化的LOS，命名为OMVSBpPagL。百日咳OMVSBpPagL。用于小鼠鼻内百日咳杆菌(In.)挑战模型，以检查其在通过In交付时的保护能力。路线。用亚致死剂量百日咳杆菌攻击免疫BALB/c小鼠。免疫动物与PBS处理组之间有显著差异(P<；0.001)。在OMVSBpPagL免疫的小鼠中观察到了足够的清除率(p<；0.005)。以及野生型OMV。根据世界卫生组织的标准，所有接受测试的OMV制剂都是无毒的；然而，OMVSBpPagL在给药后3天几乎没有体重减轻，表明与野生型OMV相比，毒性较小。诱导IL-6和IL-1在肺组织的表达。从百日咳杆菌获得的OMVSBpPagL与野生型OMV相比，其内毒素活性较低，在小鼠模型中保持保护能力，因此OMVSBpPagL似乎是开发新型多抗原疫苗的有趣候选者。(C)2010爱思唯尔有限公司。保留所有权利。
In an effort to devise a safer and effective pertussis acelullar vaccine, outer membrane vesicles (OMVs) were engineered to decrease their endotoxicity. The pagL gene from Bordetella bronchiseptica, which encodes a lipid A 3-deacylase, was expressed in Bordetella pertussis strain Tohama I. The resulting OMVs, designated OMVSBpPagL, contain tetra- instead of penta-acylated LOS, in addition to pertussis surface immunogens such as pertactin and pertussis toxin, as the wild type OMVs. The characterized pertussis OMVSBpPagL. were used in murine B. pertussis intranasal (in.) challenge model to examine their protective capacity when delivered by in. routes. Immunized BALB/c mice were challenged with sublethal doses of B. pertussis. Significant differences between immunized animals and the PBS treated group were observed (p < 0.001). Adequate elimination rates (p < 0.005) were observed in mice immunized either with OMVSBpPagL. and wild type OMVs. All OMV preparations tested were non toxic according to WHO criteria; however, OMVSBpPagL displayed almost no weight loss at 3 days post administration, indicating less toxicity when compared with wild type OMVs. Induction of IL6- and IL1-expression in lung after in. delivery as well as neutrophil recruitment to airways showed coincident results, with a lower induction of the proinflammatory cytokines and lower recruitment in the case of OMVSBpPagL compared to wild type OMVs.Given their lower endotoxic activity and retained protective capacity in the mouse model, OMVSBpPagL obtained from B. pertussis seem as interesting candidates to be considered for the development of novel multi-antigen vaccine. (C) 2010 Elsevier Ltd. All rights reserved.