Longitudinal Analysis of the Human Antibody Response to Chikungunya Virus Infection: Implications for Serodiagnosis and Vaccine Development
Longitudinal Analysis of the Human Antibody Response to Chikungunya Virus Infection: Implications for Serodiagnosis and Vaccine Development
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DOI：
10.1128/jvi.01780-12
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发表时间：
2012-12-01
影响因子：
5.4
通讯作者：
Ng, Lisa F. P.
中科院分区：
文献类型：
--
作者：
Kam, Yiu-Wing;Lee, Wendy W. L.;Ng, Lisa F. P.
基孔肯雅病毒（CHIKV）是一种甲病毒，可引起人类慢性和失能性关节痛。尽管先前的研究表明，在感染期间和感染后会产生针对该病毒的抗体，但针对CHIKV的抗体应答的精细特异性尚不清楚。在这里，使用感染后不同时间的患者血浆，我们表征了针对病毒各种蛋白质的抗体反应。我们已经表明，E2和E3糖蛋白以及衣壳和nsP 3蛋白是抗CHIKV抗体应答的靶标。此外，我们已经鉴定了这些蛋白质中含有抗CHIKV抗体识别的线性表位的不同区域，并确定了它们的结构定位。数据还说明了E2糖蛋白处的单个K（252）Q氨基酸变化的影响，由于表位-抗体结合能力的变化，其能够影响抗体结合以及抗体与表位之间的相互作用。这项研究提供了重要的知识，不仅有助于理解对CHIKV感染的免疫反应，而且还为现代疫苗开发的设计提供了新的知识。此外，这些病原体特异性表位可用于未来的血清流行病学研究，这些研究将揭示人类免疫和保护免受CHIKV疾病的分子机制。
Chikungunya virus (CHIKV) is an alphavirus which causes chronic and incapacitating arthralgia in humans. Although previous studies have shown that antibodies against the virus are produced during and after infection, the fine specificity of the antibody response against CHIKV is not known. Here, using plasma from patients at different times postinfection, we characterized the antibody response against various proteins of the virus. We have shown that the E2 and E3 glycoproteins and the capsid and nsP3 proteins are targets of the anti-CHIKV antibody response. Moreover, we have identified the different regions in these proteins which contain the linear epitopes recognized by the anti-CHIKV antibodies and determined their structural localization. Data also illustrated the effect of a single K(252)Q amino acid change at the E2 glycoprotein that was able to influence antibody binding and interaction between the antibodies and epitope because of the changes of epitope-antibody binding capacity. This study provides important knowledge that will not only aid in the understanding of the immune response to CHIKV infection but also provide new knowledge in the design of modern vaccine development. Furthermore, these pathogen-specific epitopes could be used for future seroepidemiological studies that will unravel the molecular mechanisms of human immunity and protection from CHIKV disease.