中美科学家合作研发出高效抗MERS病毒抗体

Sun

　中新社上海6月15日电 (黄文发 鲍笑寒)复旦大学15日在上海宣布，该校与美国国立卫生院的科研团队已成功开发出针对中东呼吸综合征(MERS)病毒的抗体“m336”，且动物实验非常有效。

　　这项成果由复旦大学医学分子病毒学教育部/卫生部重点实验室姜世勃团队与美国国立卫生院Dr. Dimitrov团队合作完成。

　　该抗体是目前针对MERS病毒最好的治疗药物之一，具有极强的病毒中和活性，与该病毒的结合亲和力常数达到“皮摩尔”级别。体外实验亦显示，该抗体针对假病毒的中和活性达到0.005微克/毫升，针对活病毒的中和活性达到0.07微克/毫升。该成果发表在国际病毒学专业顶尖杂志《Journal of Virology》上。

　　广东省防控MERS疫情专家钟南山院士日前接受媒体采访时指出，该病毒在体内有很高的病毒载量，靠抗体杀死病毒比较有效，呼吁能尽快进行抗体“m336”的临床试验。

　　此前，姜世勃团队已研发出具有国际领先水平的抗MERS多肽抑制剂(HR2P-M2)，动物实验的结果显示使用鼻道给药，可明显降低已感染动物肺部的病毒载量。

　　姜世勃认为，目前已发现该多肽与“m336”抗体联合使用将会产生更好的协同效果，因此在疫情紧急及征得患者或密切接触者同意的情况下，“m336”抗体可与多肽抑制剂(HR2P-M2)共同用于MERS病毒感染的防治，以挽救患者的生命。鉴于“HR2P-M2”多肽的进展更快，除了尽快进行抗体“m336”的临床试验外，也应尽快进行“HR2P-M2”多肽的临床试验。

　　据介绍，早在2012年，姜世勃教授及其课题组即关注MERS病毒发展。在SARS爆发期间，姜世勃团队曾率先在国际顶尖医学杂志《Lancet》上报道了抗SARS的C-多肽。(完)

原文链接：http://www.chinanews.com/jk/2015/06-15/7345475.shtml

bigben446

【标题】：Exceptionally potent neutralization of Middle East respiratory syndrome coronavirus by human monoclonal antibodies
【作者】：Ying, T.; Du L; Ju, T. W. (...)
【来源】：J Virol, 2014, 88(14), 7796-7805
【摘要】：The recently discovered Middle East respiratory syndrome coronavirus (MERS-CoV) continues to infect humans, with high mortality. Specific, highly effective therapeutics and vaccines against the MERS-CoV are urgently needed to save human  lives and address the pandemic concerns. We identified three human monoclonal antibodies (MAbs), m336, m337, and m338, targeting the receptor (CD26/DPP4) binding domain (RBD) of the MERS-CoV spike glycoprotein from a very large naive-antibody library (containing approximately 10(11) antibodies). They bound with high affinity: equilibrium dissociation constants for the three MAbs were equal to 4.2, 9.3, and 15 nM, respectively, as measured by Biacore for Fabs binding to RBD. The avidity for IgG1 m336, m337, and m338 was even higher: 99, 820, and 560 pM, respectively. The antibodies bound to overlapping epitopes that  overlap the receptor binding site on the RBD as suggested by competition experiments and further supported by site-directed mutagenesis of the RBD and a docking model of the m336-RBD complex. The highest-affinity MAb, m336, neutralized both pseudotyped and live MERS-CoV with exceptional potency, 50% neutralization at 0.005 and 0.07 mug/ml, respectively, likely by competing with DPP4 for binding to the S glycoprotein. The exceptionally high neutralization activity of these antibodies and especially m336 suggests that they have great potential for prophylaxis and therapy of MERS-CoV infection in humans and as a tool for development of vaccine immunogens. The rapid identification (within several weeks) of potent MAbs suggests a possibility to use the new large antibody library and related methodology for a quick response to the public threat resulting from emerging coronaviruses. Importance: A novel human coronavirus, the Middle East respiratory syndrome coronavirus (MERS-CoV), was found to infect humans with a high mortality rate in 2012, just 1 decade after the appearance of the first highly pathogenic coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV). There are no effective therapeutics  available. It is highly desirable to find an approach for rapidly developing potent therapeutics against MERS-CoV, which not only can be implemented for MERS  treatment but also can help to develop a platform strategy to combat future emerging coronaviruses. We report here the identification of human monoclonal antibodies (MAbs) from a large nonimmune antibody library that target MERS-CoV. One of the antibodies, m336, neutralized the virus with exceptional potency. It therefore may have great potential as a candidate therapeutic and as a reagent to facilitate the development of vaccines against MERS-CoV.