Protection against Lethal Leptospirosis after Vaccination with LipL32 Coupled or Coadministered with the B Subunit of Escherichia coli Heat-Labile Enterotoxin

Protection against Lethal Leptospirosis after Vaccination with LipL32 Coupled or Coadministered with the B Subunit of Escherichia coli Heat-Labile Enterotoxin
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DOI:
10.1128/cvi.05720-11
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发表时间:
2012-05-01
影响因子:
--
通讯作者:
Dellagostin, Odir A.
Dellagostin, Odir A.
中科院分区:
生物3区
文献类型:
--
作者:
Grassmann, Andre A.;Felix, Samuel R.;Dellagostin, Odir A.

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钩端螺旋体病是一种世界性的人畜共患病,目前缺乏有效、安全和交叉保护的疫苗。LipL32是钩端螺旋体所有致病性物种中存在的最丰富、最具免疫原性和最保守的表面脂蛋白,是用于重组疫苗的有希望的抗原候选物。然而,几项研究报告了缺乏保护时,这种蛋白质被用作亚单位疫苗。为了增强免疫应答,我们在钩端螺旋体病的仓鼠模型中使用与大肠杆菌不耐热肠毒素(LTB)的B亚基偶联或共同施用的LipL 32。在用5x 50%致死剂量(LD 50)的问号钩端螺旋体同源攻击后,用LipL 32与LTB和LTB::LipL 32共同施用的疫苗接种的动物具有比来自对照组的动物显著更高的存活率(P < 0.05)。这是第一次报告的保护性免疫反应提供的亚单位疫苗使用LipL32,并代表了一个重要的贡献,对开发改进的钩端螺旋体病疫苗。
Leptospirosis, a worldwide zoonosis, lacks an effective, safe, and cross-protective vaccine. LipL32, the most abundant, immunogenic, and conserved surface lipoprotein present in all pathogenic species of Leptospira, is a promising antigen candidate for a recombinant vaccine. However, several studies have reported a lack of protection when this protein is used as a subunit vaccine. In an attempt to enhance the immune response, we used LipL32 coupled to or coadministered with the B subunit of the Escherichia coli heat-labile enterotoxin (LTB) in a hamster model of leptospirosis. After homologous challenge with 5x the 50% lethal dose (LD50) of Leptospira interrogans, animals vaccinated with LipL32 coadministered with LTB and LTB::LipL32 had significantly higher survival rates (P < 0.05) than animals from the control group. This is the first report of a protective immune response afforded by a subunit vaccine using LipL32 and represents an important contribution toward the development of improved leptospirosis vaccines.