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Cross-reactive immune responses in mice after genetic vaccination with cDNA encoding hantavirus nucleocapsid proteins

机译:用汉坦病毒核衣壳蛋白编码基因进行基因疫苗接种后,小鼠的交叉反应免疫应答

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摘要

Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) in about 150,000 individuals in Eurasia, and several hundred cases of hantavirus pulmonary syndrome (HPS) on the American continent annually. There is consequently a need for rapid diagnostics and effective prevention of hantaviral infections. In this study we have performed DNA-vaccination of mice with full-length genes encoding the immunogenic nucleocapsid protein (NP) of Puumala (PUUV), Seoul (SEOV) and Sin Nombre virus (SNV). The antibody reactivity towards the NPs, and deleted or truncated variants thereof, were studied to localise and investigate the major polyclonal B-cell epitopes. Our findings clearly show that the antibody reactivity in each immunised mouse is unique, not only in a quantitative respect (titers) but also in cross-reactivity and most likely also in the epitope specificity. Our experimental data in combination with B-cell prediction software indicate that strong homologous virus species specific and cross-reactive epitopes are located around amino acid residue 40 in the nucleocapsid proteins.
机译:汉坦病毒在欧亚大陆约有15万人导致肾综合征出血热(HFRS),而在美洲大陆每年有数百例汉坦病毒肺综合征(HPS)。因此,需要快速诊断和有效预防汉坦病毒感染。在这项研究中,我们用全长基因编码的小鼠进行了DNA疫苗接种,该基因编码了Puumala(PUUV),Seoul(SEOV)和Sin Nombre病毒(SNV)的免疫原性核衣壳蛋白(NP)。研究了针对NP的抗体反应性及其缺失或截短的变体,以定位和研究主要的多克隆B细胞表位。我们的发现清楚地表明,每只免疫小鼠的抗体反应性是独特的,不仅在定量方面(滴度),而且在交叉反应性上以及在表位特异性上最有可能。我们的实验数据结合B细胞预测软件表明,强同源病毒物种特异性和交叉反应性表位位于核衣壳蛋白的40号氨基酸残基周围。

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