Identification of an OmpW homologue in Burkholderia pseudomallei, a protective vaccine antigen against melioidosis
Identification of an OmpW homologue in Burkholderia pseudomallei, a protective vaccine antigen against melioidosis
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DOI：
10.1016/j.vaccine.2016.03.088
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发表时间：
2016-05-17
期刊：
影响因子：
5.5
通讯作者：
McClean, Siobhan
中科院分区：
文献类型：
--
作者：
Casey, William T.;Spink, Natasha;McClean, Siobhan
类鼻疽伯克霍尔德菌是类鼻疽病的病原体，其与一系列临床表现相关，包括败血症和致命性肺炎，并且在东南亚和北方澳大利亚流行。治疗可能具有挑战性，感染的控制涉及长期的抗生素治疗，但没有批准的疫苗可用于预防感染。我们的目的是开发和评估针对类鼻疽的预防性候选疫苗的潜力。确定的候选者是22 kDa的外膜蛋白OmpW。我们以前证明，这种蛋白质是免疫保护性的洋葱伯克霍尔德氏菌复合体（BCC）感染的小鼠模型。我们在大肠杆菌中克隆了Bp_ompW基因，并进行了原核表达和纯化。相对于对照组（25%存活率）（p < 0.05），与SAS佐剂一起施用的无内毒素蛋白质保护了Balb/C小鼠（75%存活率）。观察到强效血清学应答，IgG 2a与IgG 1的比值为6.0。此外，C57 BL/6小鼠对致死剂量的B的保护长达80天。结果表明，2D 2阳性对照组与假鼻疽疫苗组相比具有更好的免疫效果，并且超过了减毒活2D 2阳性对照组的效力。BpompW在13个测序的B中同源。表明它对B具有广泛的保护作用。假鼻疽总之，我们已经证明，BpOmpW能够诱导针对类鼻疽的保护性免疫，并且可能是有效的疫苗抗原，可能与其他亚单位抗原组合。(C)2016爱思唯尔有限公司版权所有
Burkholderia pseudomallei is the causative agent of melioidosis, which is associated with a range of clinical manifestations, including sepsis and fatal pneumonia and is endemic in Southeast Asia and Northern Australia. Treatment can be challenging and control of infection involves prolonged antibiotic therapy, yet there are no approved vaccines available to prevent infection. Our aim was to develop and assess the potential of a prophylactic vaccine candidate targeted against melioidosis. The identified candidate is the 22 kDa outer membrane protein, OmpW. We previously demonstrated that this protein was immuno-protective in mouse models of Burkholderia cepacia complex (Bcc) infections. We cloned Bp_ompW in Escherichia coli, expressed and purified the protein. Endotoxin free protein administered with SAS adjuvant protected Balb/C mice (75% survival) relative to controls (25% survival) (p < 0.05). A potent serological response was observed with IgG2a to IgG1 ratio of 6.0. Furthermore C57BL/6 mice were protected for up to 80 days against a lethal dose of B. pseudomallei and surpassed the efficacy of the live attenuated 2D2 positive control. BpompW is homologous across thirteen sequenced B. pseudomallei strains, indicating that it should be broadly protective against B. pseudomallei. In conclusion, we have demonstrated that BpOmpW is able to induce protective immunity against melioidosis and is likely to be an effective vaccine antigen, possibly in combination with other subunit antigens. (C) 2016 Elsevier Ltd. All rights reserved.