Truncated Recombinant Dobrava Hantavirus Nucleocapsid Proteins Induce Strong, Long-Lasting Immune Responses in Mice
Truncated Recombinant Dobrava Hantavirus Nucleocapsid Proteins Induce Strong, Long-Lasting Immune Responses in Mice
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截短的重组多布拉瓦汉坦病毒核衣壳蛋白在小鼠中诱导强烈、持久的免疫反应
DOI：
10.1159/000093454
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发表时间：
2006
期刊：
影响因子：
4.6
通讯作者：
M. Van Ranst
中科院分区：
文献类型：
--
作者：
P. Maes;E. Keyaerts;V. Bonnet;J. Clement;T. Avšič;A. Robert;M. Van Ranst
我们描述了Dobrava汉坦病毒（DOBV）核衣壳蛋白的克隆和表达，以及由前118个N-末端氨基酸组成的截短形式，以及这些E. coli ICONE 200表达的重组蛋白（rNp）诱导小鼠产生抗DOBV的保护性免疫应答。作为替代载体蛋白，来自肺炎克雷伯氏菌（Klebsiella pneumoniae）的外膜蛋白A（rP 40）已经偶联到不同的rNp构建体。经三次rNp免疫后，所有重组蛋白均具有高度免疫原性。免疫导致诱导强烈的NP特异性IgG应答，其中IgG 1占优势，超过IgG 2b和IgG 2a，表明混合的Th 1/Th 2细胞参与。未检测到特异性IgG 3应答。与rP 40缀合的构建体相比，用不含rP 40的重组DOBV rNp免疫的小鼠显示出较低的核衣壳特异性抗体应答，但发现所有小鼠都被保护免受DOBV攻击。我们的研究结果表明，rNP构建体耦合到rP 40，代表有前途的候选疫苗。
We describe the cloning and expression of Dobrava hantavirus (DOBV) nucleocapsid proteins and a truncated form consisting of the first 118 N-terminal amino acids, and the capacity of these E. coli ICONE 200-expressed recombinant proteins (rNp) to induce a protective immune response against DOBV in mice. As an alternative carrier protein, the outer membrane protein A derived from Klebsiella pneumoniae (rP40) has been coupled to different rNp constructs. All recombinant proteins were found to be highly immunogenic after three immunizations of rNp. The immunizations resulted in the induction of a strong Np-specific IgG response with a predominance of IgG1 over IgG2b and IgG2a, suggesting a mixed Th1/Th2 cell involvement. A specific IgG3 response could not be detected. Mice immunized with recombinant DOBV rNp without rP40 showed lower nucleocapsid-specific antibody responses in comparison with the rP40-conjugated constructs, but all mice were found to be protected against DOBV challenge. Our results indicate that the rNp constructs coupled to rP40, represent promising vaccine candidates.