Neutralizing antibodies against the preactive form of respiratory syncytial virus fusion protein offer unique possibilities for clinical intervention
Neutralizing antibodies against the preactive form of respiratory syncytial virus fusion protein offer unique possibilities for clinical intervention
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DOI：
10.1073/pnas.1115941109
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发表时间：
2012-02-21
影响因子：
11.1
通讯作者：
Palomo, Concepcion
中科院分区：
文献类型：
--
作者：
Magro, Margarita;Mas, Vicente;Palomo, Concepcion
人呼吸道合胞病毒（hRSV）是全球儿童呼吸道感染最重要的病毒病原体。目前唯一可用的特异性治疗方法是一种针对F糖蛋白的人源化单克隆抗体（帕利珠单抗），预防性用于发生严重hRSV感染风险极高的儿童。帕利珠单抗与目前所描述的大多数抗F抗体一样，识别hRSV_F可折叠的两种构象所共有的一个表位，即亚稳态的融合前形式和高度稳定的融合后构象。我们现在描述了一类独特的针对该蛋白融合前形式的抗体，它们在针对表达hRSV_F的痘苗病毒重组体所产生的兔血清或一种人免疫球蛋白制剂（Respigam，在帕利珠单抗之前用于预防）的中和活性中占大部分。因此，这些抗体为针对hRSV的免疫干预提供了独特的可能性，并且应在hRSV疫苗试验中评估它们的产生。
Human respiratory syncytial virus (hRSV) is the most important viral agent of pediatric respiratory infections worldwide. The only specific treatment available today is a humanized monoclonal antibody (Palivizumab) directed against the F glycoprotein, administered prophylactically to children at very high risk of severe hRSV infections. Palivizumab, as most anti-F antibodies so far described, recognizes an epitope that is shared by the two conformations in which hRSV_F can fold, the metastable prefusion form and the highly stable postfusion conformation. We now describe a unique class of antibodies specific for the prefusion form of this protein that account for most of the neutralizing activity of either a rabbit serum raised against a vaccinia virus recombinant expressing hRSV_F or a human Ig preparation (Respigam), which was used for prophylaxis before Palivizumab. These antibodies therefore offer unique possibilities for immune intervention against hRSV, and their production should be assessed in trials of hRSV vaccines.