Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody.

The respiratory syncytial virus (RSV) fusion (F) glycoprotein prefusion conformation is the target of most RSV-neutralizing activity in human sera, but its metastability has hindered characterization. To overcome this obstacle, we identified prefusion-specific antibodies which were substantially more potent than the prophylactic antibody palivizumab. The co-crystal structure for one of these antibodies, D25, in complex with the F glycoprotein revealed that D25 locks F in its prefusion state by binding to a quaternary epitope at the trimer apex. Electron microscopy showed two other antibodies, AM22 and 5C4, also bind to the newly identified site of vulnerability, which we named antigenic site Ø. These studies should enable design of improved vaccine antigens and guide new approaches for passive prevention of RSV-induced disease.

呼吸道合胞病毒（RSV）融合（F）糖蛋白的预融合构象是人类血清中大多数RSV中和活性的靶点，但其亚稳定性阻碍了对其特性的研究。为克服这一障碍，我们鉴定出了对预融合状态特异性的抗体，这些抗体比预防性抗体帕利珠单抗的效力强得多。其中一种抗体D25与F糖蛋白形成的共晶结构显示，D25通过与三聚体顶端的一个四级表位结合，将F锁定在其预融合状态。电子显微镜显示另外两种抗体AM22和5C4也结合到这个新发现的脆弱位点，我们将其命名为抗原位点Ø。这些研究应能使改进的疫苗抗原得以设计，并为被动预防RSV诱发的疾病提供新的方法指导。