Enzyme-linked Immunosorbent assays using novel Japanese encephalitis virus antigen improve the accuracy of clinical diagnosis of flavivirus infections
Enzyme-linked Immunosorbent assays using novel Japanese encephalitis virus antigen improve the accuracy of clinical diagnosis of flavivirus infections
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DOI：
10.1128/cvi.00004-08
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发表时间：
2008-05-01
影响因子：
--
通讯作者：
Chang, Gwong-Jen J.
中科院分区：
文献类型：
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作者：
Chiou, Shyan-Song;Crill, Wayne D.;Chang, Gwong-Jen J.
黄病毒感染引起的交叉反应抗体混淆了血清学诊断和发病机制，特别是在由抗原性密切相关但不同的黄病毒引起的继发感染中。包膜(E)糖蛋白融合肽含有免疫优势的交叉反应决定簇。用重组乙型脑炎病毒(JEV)前膜和产生JEV病毒样颗粒(VLP)的E表达载体，G106K-L107D(KD)双突变VLP与一组黄病毒鼠源单抗的交叉反应显著降低。为了比较JEV野生型(WT)和KD VLP在酶联免疫吸附试验中作为血清学诊断抗原的准确性，对近期黄病毒感染患者的人血清板进行了分析。统计分析表明，在血清稀释度为1：4000(似然比=2.74[WT]和22[KD])时，通过检测免疫球蛋白M抗体，在准确确定WT和KD抗原之间当前JEV感染方面存在显著差异。交叉反应减少型抗原的应用和持续发展应该会改善黄病毒感染的血清诊断和疾病负担的估计。
The cross-reactive antibodies induced by flavivirus infections confound serodiagnosis and pathogenesis, especially in secondary infections caused by antigenically closely related yet distinct flaviviruses. The envelope (E) glycoprotein fusion peptide contains immunodominant cross-reactive determinants. Using a recombinant Japanese encephalitis virus (JEV) premembrane and E expression plasmid producing JEV virus-like particles (VLPs), dramatic reductions in cross-reactivity were produced by the G106K-L107D (KD) double-mutant VLP against a panel of flavivirus murine monoclonal antibodies. Human serum panels from patients with recent flavivirus infections were analyzed to compare the accuracy of JEV wild-type (WT) and KD VLPs as serodiagnostic antigens in enzyme-linked immunosorbent assays. Statistical analysis demonstrated significant differences in assay performances for accurate determination of current JEV infections between WT and KD antigens by detecting immunoglobulin M antibodies at a serum dilution of 1: 4,000 (likelihood ratios = 2.74 [WT] and 22 [KD]). The application and continued development of cross-reactivity-reduced antigens should improve both flavivirus infection serodiagnosis and estimates of disease burden.