Recombinant Streptococcus equi proteins protect mice in challenge experiments and induce immune response in horses

Recombinant Streptococcus equi proteins protect mice in challenge experiments and induce immune response in horses
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DOI:
10.1128/iai.72.6.3228-3236.2004
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发表时间:
2004-06-01
影响因子:
3.1
通讯作者:
Flock, JI
Flock, JI
中科院分区:
医学2区
文献类型:
--
作者:
Flock, M;Jacobsson, K;Flock, JI

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马链球菌亚种马(窒息)感染后,发现马血清中抗三种先前表征的蛋白质(FNZ(细胞表面结合纤连蛋白结合蛋白)、SFS(分泌型纤连蛋白结合蛋白)和EAG(α 2-巨球蛋白、白蛋白和免疫球蛋白G [IgG]结合蛋白)的抗体滴度显著增加。等。为了评估用这三种蛋白质接种的保护效力,利用马窒息的小鼠模型。在用S.马链球菌等。使用的佐剂是Etx B,大肠杆菌不耐热肠毒素B亚基的重组形式。结果表明,鼻内定植的S。马链球菌与模拟疫苗接种对照组相比,疫苗接种后由于感染引起的马体重和体重减轻显著减少。鼻内接种后的这种效应比皮下接种后更明显;鼻内接种后几乎完全根除了鼻内定植(P < 0.001)。当相同的抗原给药鼻内和皮下健康马,显着的粘膜伊加和血清IgG抗体反应FNZ和EAG。当EtxB用作佐剂时,抗体应答增强。未观察到抗原或EtxB的不良反应。因此,FNZ和EAG结合EtxB是有效和安全的抗窒息疫苗的有希望的候选者。
Horses that have undergone infection caused by Streptococcus equi subspecies equi (strangles) were found to have significantly increased serum antibody titers against three previously characterized proteins, FNZ (cell surface-bound fibronectin binding protein), SFS (secreted fibronectin binding protein), and EAG (alpha(2)-macroglobulin, albumin, and immunoglobulin G [IgG] binding protein) from S. equi. To assess the protective efficacy of vaccination with these three proteins, a mouse model of equine strangles was utilized. Parts of the three recombinant proteins were used to immunize mice, either subcutaneously or intranasally, prior to nasal challenge with S. equi subsp. equi. The adjuvant used was EtxB, a recombinant form of the B subunit of Escherichia coli heat-labile enterotoxin. It was shown that nasal colonization of S. equi subsp. equi and weight loss due to infection were significantly reduced after vaccination compared with a mock-vaccinated control group. This effect was more pronounced after intranasal vaccination than after subcutaneous vaccination; nearly complete eradication of nasal colonization was obtained after intranasal vaccination (P < 0.001). When the same antigens were administered both intranasally and subcutaneously to healthy horses, significant mucosal IgA and serum IgG antibody responses against FNZ and EAG were obtained. The antibody response was enhanced when EtxB was used as an adjuvant. No adverse effects of the antigens or EtxB were observed. Thus, FNZ and EAG in conjunction with EtxB are promising candidates for an efficacious and safe vaccine against strangles.