Evaluation of candidate vaccine approaches for MERS-CoV.
Evaluation of candidate vaccine approaches for MERS-CoV.
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DOI：
10.1038/ncomms8712
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发表时间：
2015-07-28
影响因子：
16.6
通讯作者：
Graham BS
中科院分区：
文献类型：
--
作者：
Wang L;Shi W;Joyce MG;Modjarrad K;Zhang Y;Leung K;Lees CR;Zhou T;Yassine HM;Kanekiyo M;Yang ZY;Chen X;Becker MM;Freeman M;Vogel L;Johnson JC;Olinger G;Todd JP;Bagci U;Solomon J;Mollura DJ;Hensley L;Jahrling P;Denison MR;Rao SS;Subbarao K;Kwong PD;Mascola JR;Kong WP;Graham BS
中东呼吸综合征冠状病毒（MERS-CoV）作为严重呼吸道疾病的一种病因的出现，凸显了开发冠状病毒疫苗的有效方法的必要性。仅关注病毒刺突(S)糖蛋白的受体结合域（RBD）可能无法优化中和抗体（NAb）反应。本研究表明，基于全长S DNA和S1亚基蛋白的免疫原在小鼠和非人灵长类动物中对几种MERS-CoV毒株具有强大的血清中和活性。小鼠单克隆抗体的血清学分析和分离表明，免疫可诱导针对RBD和非RBD部分S1和S2亚基的nab。通过解决NAb-RBD复合物的原子结构，通过对中和逃逸病毒的测序以及构建用于血清学分析的MERS-CoV S变体，证明了多种中和机制。通过计算机断层扫描评估，恒河猴免疫接种可保护其免受MERS-CoV诱导的放射性肺炎，支持该策略作为MERS-CoV疫苗开发的一种有希望的方法。本文的在线版本（doi:10.1038/ncomms8712）包含补充材料，可供授权用户使用。针对中东呼吸综合征冠状病毒（MERS-CoV）的疫苗需求尚未得到满足。在这里，作者报告了在小鼠和灵长类动物中建立和评估一系列中东呼吸综合征冠状病毒免疫原，并表明它们可以作为疫苗开发的有希望的线索。本文的在线版本（doi:10.1038/ncomms8712）包含补充材料，可供授权用户使用。
The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanisms were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development. The online version of this article (doi:10.1038/ncomms8712) contains supplementary material, which is available to authorized users. Unmet need exists for a vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV). Here the authors report the establishment and evaluation, in mice and primates, of a series of MERS-CoV immunogens and show that they can serve as promising leads for vaccine development. The online version of this article (doi:10.1038/ncomms8712) contains supplementary material, which is available to authorized users.