Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection.
Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection.
复制标题
种系样中和人单克隆抗体的被动转移可保护转基因小鼠免受致命的中东呼吸综合征冠状病毒感染
DOI：
10.1038/srep31629
复制
发表时间：
2016-08-19
影响因子：
4.6
通讯作者：
Tseng CT
中科院分区：
文献类型：
--
作者：
Agrawal AS;Ying T;Tao X;Garron T;Algaissi A;Wang Y;Wang L;Peng BH;Jiang S;Dimitrov DS;Tseng CT
中东呼吸综合征冠状病毒(MERS-CoV)曾多次在阿拉伯半岛引发疫情。到目前为止，还没有获得批准的医学对策(MCM)来对抗MERS冠状病毒感染。包括MERS冠状病毒M336在内的几种中和性人源单抗(MAbs)已被选为MERS冠状病毒的MCM。然而，由于缺乏一个强大的动物模型来概括人类感染的发病率和死亡率，它们的临床开发受到了阻碍。我们使用对MERS冠状病毒感染和疾病高度敏感的特征良好的转基因小鼠来评估M336的预防和治疗效果。我们发现，在致命的MERS冠状病毒攻击之前或之后使用m336治疗的小鼠得到了完全保护，而对照组小鼠在感染后几天内体重大幅下降和均匀死亡。综上所述，这些结果支持进一步开发M336和其他人类单抗作为治疗MERS冠状病毒感染的潜在药物。
Middle East Respiratory Syndrome coronavirus (MERS-CoV) has repeatedly caused outbreaks in the Arabian Peninsula. To date, no approved medical countermeasures (MCM) are available to combat MERS-CoV infections. Several neutralizing human monoclonal antibodies (mAbs), including m336, a germline-like human mAb, have been chosen as promising MCM for MERS-CoV. However, their clinical development has been hindered by the lack of a robust animal model that recapitulate the morbidity and mortality of human infections. We assessed the prophylactic and therapeutic efficacy of m336 by using well-characterized transgenic mice shown to be highly sensitive to MERS-CoV infection and disease. We found that mice treated with m336 prior to or post lethal MERS-CoV challenging were fully protected, compared to control mice which sufferered from profound weight loss and uniform death within days after infection. Taken together, these results support further development of m336 and other human monoclonal antibodies as potential therapeutics for MERS-CoV infection.