Evaluation of serologic and antigenic relationships between middle eastern respiratory syndrome coronavirus and other coronaviruses to develop vaccine platforms for the rapid response to emerging coronaviruses.
Evaluation of serologic and antigenic relationships between middle eastern respiratory syndrome coronavirus and other coronaviruses to develop vaccine platforms for the rapid response to emerging coronaviruses.
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DOI：
10.1093/infdis/jit609
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发表时间：
2014-04-01
期刊：
影响因子：
--
通讯作者：
Baric RS
中科院分区：
文献类型：
--
作者：
Agnihothram S;Gopal R;Yount BL Jr;Donaldson EF;Menachery VD;Graham RL;Scobey TD;Gralinski LE;Denison MR;Zambon M;Baric RS
背景：中东呼吸综合征冠状病毒（MERS-CoV）出现于2012年，引起严重急性呼吸道疾病和肺炎，迄今为止136例病例中死亡率为44%。 设计疫苗以限制病毒传播或诊断测试以跟踪新出现的毒株需要了解MERS CoV和其他CoV之间的抗原和血清学关系。 方法：使用合成基因组学和委内瑞拉马脑炎病毒复制子（VRP）表达刺突蛋白和核衣壳蛋白从MERS冠状病毒和其他人类和蝙蝠冠状病毒，我们的特点的抗原反应（使用蛋白质印迹和酶联免疫吸附试验）和血清学反应（使用中和试验）对2 MERS冠状病毒分离株与其他人类和蝙蝠冠状病毒。 结果：针对刺突糖蛋白的血清学和中和反应主要是菌株特异性的，在亚组内或亚组间的交叉反应水平非常低。 在亚组内但不跨亚组的CoV N蛋白与MERS-CoV分离株共享交叉反应性表位。我们的研究结果进行了验证，使用从MERS冠状病毒（NA 01）感染患者的恢复期血清标本和人抗SARS-CoV，人冠状病毒NL 63，和人冠状病毒OC 43。 结论：新冠病毒的疫苗设计应包括嵌合刺突蛋白，该蛋白含有来自不同亚群的多个病毒株的中和表位，以减少免疫病理学，诊断平台应包括一组来自不同遗传学CoV的核衣壳和刺突蛋白。
Background. Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012, causing severe acute respiratory disease and pneumonia, with 44% mortality among 136 cases to date. Design of vaccines to limit the virus spread or diagnostic tests to track newly emerging strains requires knowledge of antigenic and serologic relationships between MERS-CoV and other CoVs. Methods. Using synthetic genomics and Venezuelan equine encephalitis virus replicons (VRPs) expressing spike and nucleocapsid proteins from MERS-CoV and other human and bat CoVs, we characterize the antigenic responses (using Western blot and enzyme-linked immunosorbent assay) and serologic responses (using neutralization assays) against 2 MERS-CoV isolates in comparison with those of other human and bat CoVs. Results. Serologic and neutralization responses against the spike glycoprotein were primarily strain specific, with a very low level of cross-reactivity within or across subgroups. CoV N proteins within but not across subgroups share cross-reactive epitopes with MERS-CoV isolates. Our findings were validated using a convalescent-phase serum specimen from a patient infected with MERS-CoV (NA 01) and human antiserum against SARS-CoV, human CoV NL63, and human CoV OC43. Conclusions. Vaccine design for emerging CoVs should involve chimeric spike protein containing neutralizing epitopes from multiple virus strains across subgroups to reduce immune pathology, and a diagnostic platform should include a panel of nucleocapsid and spike proteins from phylogenetically distinct CoVs.
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