Human monoclonal antibodies to SARS-coronavirus inhibit infection by different mechanisms.

Human monoclonal antibodies to SARS-coronavirus inhibit infection by different mechanisms.
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DOI:
10.1016/j.virol.2009.07.028
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发表时间:
2009-11-10
期刊:
影响因子:
3.7
通讯作者:
Prabhakar BS
Prabhakar BS
中科院分区:
医学3区
文献类型:
--
作者:
Coughlin MM;Babcook J;Prabhakar BS

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SARS-CoV引起急性感染,使靶向被动免疫疗法成为一种有吸引力的治疗策略。我们以前产生的人单克隆抗体特异性的SARS-CoV S蛋白的S1区。这些mAb结合受体结合域(RBD)内或RBD上游的表位。我们表明,识别RBD内表位的mAb通过阻止病毒附着到细胞受体来抑制感染。一种mAb结合RBD的上游,并通过抑制结合后事件来防止病毒进入。对几种mAb的评价表明,当单独使用时,mAb选择逃逸突变体的能力不同。然而,抗体的混合物可以有效地中和一系列突变病毒。这些数据强烈表明,含有识别不同区域并靶向病毒进入中的一个以上步骤的抗体的混合物可能在中和病毒和抑制逃逸突变体的产生方面更有效,因此可能构成高效的被动免疫疗法。
SARS-CoV causes an acute infection making targeted passive immunotherapy an attractive treatment strategy. We previously generated human mAbs specific to the S1 region of SARS-CoV S protein. These mAbs bind epitopes within the receptor binding domain (RBD) or upstream of the RBD. We show that mAbs recognizing epitopes within the RBD inhibit infection by preventing viral attachment to the cellular receptor. One mAb binds upstream of the RBD and prevents viral entry by inhibiting a post-binding event. Evaluation of several mAbs demonstrated varying ability of the mAbs to select escape mutants when used individually. However, a mixture of antibodies could effectively neutralize a range of mutant viruses. These data strongly suggest that a mixture containing antibodies recognizing distinct regions and targeting more than one step in viral entry is likely to be more effective in neutralizing the virus and suppressing the generation of escape mutants, and thus potentially constitute a highly effective passive immunotherapy.
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