Early neutralizing IgG response to Chikungunya virus in infected patients targets a dominant linear epitope on the E2 glycoprotein.
Early neutralizing IgG response to Chikungunya virus in infected patients targets a dominant linear epitope on the E2 glycoprotein.
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DOI：
10.1002/emmm.201200213
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发表时间：
2012-04
影响因子：
11.1
通讯作者：
Ng, Lisa F. P.
中科院分区：
文献类型：
--
作者：
Kam, Yiu-Wing;Lum, Fok-Moon;Teo, Teck-Hui;Lee, Wendy W. L.;Simarmata, Diane;Harjanto, Sumitro;Chua, Chong-Long;Chan, Yoke-Fun;Wee, Jin-Kiat;Chow, Angela;Lin, Raymond T. P.;Leo, Yee-Sin;Le Grand, Roger;Sam, I-Ching;Tong, Joo-Chuan;Roques, Pierre;Wiesmueller, Karl-Heinz;Renia, Laurent;Roetzschke, Olaf;Ng, Lisa F. P.
基孔肯雅病毒（CHIKV）和相关的虫媒病毒是造成大规模流行病爆发的原因，具有严重的经济和社会影响。控制病毒增殖和传播的免疫机制尚不清楚。在这里，我们研究了感染患者中针对CHIKV表面抗原的抗体应答。利用在早期恢复期期间获得的血浆样品，我们表明天然获得的IgG应答主要由主要对单一线性表位“E2 EP 3”特异性的IgG 3抗体主导。E2 EP 3位于E2糖蛋白的N-末端，并显著暴露在病毒包膜上。E2 EP 3特异性抗体是中和性的，并且它们从血浆中的去除使CHIKV特异性抗体滴度降低高达80%。在不同患者群组中和在非人灵长类动物中筛选E2 EP 3证明了该表位作为CHIKV感染的良好血清学检测标志物的价值，其已经处于早期阶段。通过E2 EP 3肽接种的小鼠被保护免受CHIKV，具有减少的病毒血症和关节炎症，为设计针对关节痛诱导的CHIKV和其他甲病毒的有效疫苗提供了临床前基础。
Chikungunya virus (CHIKV) and related arboviruses have been responsible for large epidemic outbreaks with serious economic and social impact. The immune mechanisms, which control viral multiplication and dissemination, are not yet known. Here, we studied the antibody response against the CHIKV surface antigens in infected patients. With plasma samples obtained during the early convalescent phase, we showed that the naturally-acquired IgG response is dominated by IgG3 antibodies specific mostly for a single linear epitope ‘E2EP3’. E2EP3 is located at the N-terminus of the E2 glycoprotein and prominently exposed on the viral envelope. E2EP3-specific antibodies are neutralizing and their removal from the plasma reduced the CHIKV-specific antibody titer by up to 80%. Screening of E2EP3 across different patient cohorts and in non-human primates demonstrated the value of this epitope as a good serology detection marker for CHIKV infection already at an early stage. Mice vaccinated by E2EP3 peptides were protected against CHIKV with reduced viremia and joint inflammation, providing a pre-clinical basis for the design of effective vaccine against arthralgia-inducing CHIKV and other alphaviruses.
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影响因子：
3.8
作者：
Hunt, Ann R.;Frederickson, Shana;Blair, Carol D.
通讯作者：
Blair, Carol D.
影响因子：
5.4
作者：
Kowalzik, Stefan;Xuan, Nghia Vu;Bodem, Jochen
通讯作者：
Bodem, Jochen
影响因子：
5.2
作者：
Han T;Marasco WA
通讯作者：
Marasco WA
影响因子：
2.4
作者：
Cho B;Jeon BY;Kim J;Noh J;Kim J;Park M;Park S
通讯作者：
Park S
影响因子：
0.8
作者：
Englund, J. A.
通讯作者：
Englund, J. A.