Infectious Diseases and Vaccines Discovery, Merck & Co., Inc., West Point, PA, USA.
Discovery Biologics, Merck & Co., Inc., Boston, MA, USA.
Nat Commun. 2022 May 10;13(1):2546. doi: 10.1038/s41467-022-30205-x.
Human metapneumovirus (hMPV) belongs to the Pneumoviridae family and is closely related to respiratory syncytial virus (RSV). The surface fusion (F) glycoprotein mediates viral fusion and is the primary target of neutralizing antibodies against hMPV. Here we report 113 hMPV-F specific monoclonal antibodies (mAbs) isolated from memory B cells of human donors. We characterize the antibodies' germline usage, epitopes, neutralization potencies, and binding specificities. We find that unlike RSV-F specific mAbs, antibody responses to hMPV F are less dominant against the apex of the antigen, and the majority of the potent neutralizing mAbs recognize epitopes on the side of hMPV F. Furthermore, neutralizing epitopes that differ from previously defined antigenic sites on RSV F are identified, and multiple binding modes of site V and II mAbs are discovered. Interestingly, mAbs that bind preferentially to the unprocessed prefusion F show poor neutralization potency. These results elucidate the immune recognition of hMPV infection and provide novel insights for future hMPV antibody and vaccine development.
人偏肺病毒（hMPV）属于副黏病毒科，与呼吸道合胞病毒（RSV）密切相关。表面融合（F）糖蛋白介导病毒融合，是针对 hMPV 的中和抗体的主要靶标。在此，我们报告了从人类供体的记忆 B 细胞中分离出的 113 种 hMPV-F 特异性单克隆抗体（mAb）。我们对抗体的胚系使用、表位、中和效力和结合特异性进行了表征。我们发现，与 RSV-F 特异性 mAb 不同，针对 hMPV F 的抗体反应对抗原的顶点不太占主导地位，大多数有效的中和 mAb 识别 hMPV F 侧面的表位。此外，还鉴定出与 RSV F 上先前定义的抗原位点不同的中和表位，并发现了位点 V 和 II mAb 的多种结合模式。有趣的是，优先结合未加工的预融合 F 的 mAb 显示出较差的中和效力。这些结果阐明了对 hMPV 感染的免疫识别，并为未来的 hMPV 抗体和疫苗开发提供了新的见解。
