Human monoclonal antibodies against highly conserved HR1 and HR2 domains of the SARS-CoV spike protein are more broadly neutralizing.
Human monoclonal antibodies against highly conserved HR1 and HR2 domains of the SARS-CoV spike protein are more broadly neutralizing.
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DOI：
10.1371/journal.pone.0050366
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Prabhakar BS
中科院分区：
文献类型：
--
作者：
Elshabrawy HA;Coughlin MM;Baker SC;Prabhakar BS
来自恢复期患者的免疫血清已被证明在治疗感染严重急性呼吸综合征病毒（SARS-CoV）的患者中是有效的，使得使用人单克隆抗体的被动免疫治疗成为SARS的有吸引力的治疗策略。以前，使用Xenomouse（Amgen不列颠哥伦比亚省公司），我们生产了一组中和人单克隆抗体（HmAbs），其可以特异性结合SARS-CoV刺突（S）糖蛋白的胞外域。一些HmAb是S1结构域特异性的，而一些不是。在这项研究中，我们描述了非S1结合中和HmAb，可以特异性结合保守的S2结构域的S蛋白。然而，与S1特异性HmAbs不同，S2特异性HmAbs可以中和表达不同S蛋白的假型病毒，所述不同S蛋白含有各种临床分离株的受体结合结构域序列。这些数据表明，结合到S蛋白的保守区域的HmAb更适合于赋予针对广泛的SARS-CoV变体的保护，并且对于产生针对其他包膜病毒的治疗性抗体或亚单位疫苗具有意义。
Immune sera from convalescent patients have been shown to be effective in the treatment of patients infected with Severe Acute Respiratory Syndrome Virus (SARS-CoV) making passive immune therapy with human monoclonal antibodies an attractive treatment strategy for SARS. Previously, using Xenomouse (Amgen British Columbia Inc), we produced a panel of neutralizing Human monoclonal antibodies (HmAbs) that could specifically bind to the ectodomain of the SARS-CoV spike (S) glycoprotein. Some of the HmAbs were S1 domain specific, while some were not. In this study, we describe non-S1 binding neutralizing HmAbs that can specifically bind to the conserved S2 domain of the S protein. However, unlike the S1 specific HmAbs, the S2 specific HmAbs can neutralize pseudotyped viruses expressing different S proteins containing receptor binding domain sequences of various clinical isolates. These data indicate that HmAbs which bind to conserved regions of the S protein are more suitable for conferring protection against a wide range of SARS-CoV variants and have implications for generating therapeutic antibodies or subunit vaccines against other enveloped viruses.
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DOI：
10.1074/jbc.m508381200
发表时间：
2006-02-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Huang IC;Bosch BJ;Li F;Li W;Lee KH;Ghiran S;Vasilieva N;Dermody TS;Harrison SC;Dormitzer PR;Farzan M;Rottier PJ;Choe H
通讯作者：
Choe H
影响因子：
3.7
作者：
Coughlin MM;Babcook J;Prabhakar BS
通讯作者：
Prabhakar BS
影响因子：
5.4
作者：
Bosch, Berend Jan;Bartelink, Willem;Rottier, Peter J. M.
通讯作者：
Rottier, Peter J. M.
影响因子：
7.6
作者：
Liu IJ;Kao CL;Hsieh SC;Wey MT;Kan LS;Wang WK
通讯作者：
Wang WK
影响因子：
3.7
作者：
Coughlin M;Lou G;Martinez O;Masterman SK;Olsen OA;Moksa AA;Farzan M;Babcook JS;Prabhakar BS
通讯作者：
Prabhakar BS