美国Adagio医疗Laura M. Walker和美国德克萨斯大学奥斯汀分校Jason S. McLellan团队合作，开发出强效中和和保护性抗人偏肺病毒 (hMPV)抗体，可靶向融合糖蛋白上的不同位点。2022年8月8日，国际知名学术期刊《免疫学》发表了这一成果。

他们使用高通量单细胞技术来探求年轻和老年供体中记忆 B 细胞对 hMPV 融合 (F) 糖蛋白的反应。在所有供体中，中和抗体反应主要针对在融合前和融合后 F 构象上表达的表位。然而，他们发现了罕见、高效的广泛中和抗体，这些抗体识别融合前特异性表位，并在结构上表征了一种针对融合前 F 三聚体顶点易损位点的抗体。此外，针对三个不同抗原位点的中和抗体的单一疗法，在小动物模型中提供了针对下呼吸道感染的强大保护。该研究为被动免疫预防提供了有希望的单克隆抗体候选物，并为hMPV疫苗免疫原的合理设计提供了信息。

据了解，hMPV是高危人群急性下呼吸道感染的主要原因，但目前还没有批准用于预防或治疗 hMPV 相关疾病的疫苗或抗病毒疗法。

附：英文原文

Title: Potently neutralizing and protective anti-human metapneumovirus antibodies target diverse sites on the fusion glycoprotein

Author: C. Garrett Rappazzo, Ching-Lin Hsieh, Scott A. Rush, Emma S. Esterman, Teresa Delgado, James C. Geoghegan, Anna Z. Wec, Mrunal Sakharkar, Vicente Más, Jason S. McLellan, Laura M. Walker

Issue&Volume: 2022-08-08

Abstract: Human metapneumovirus (hMPV) is a leading cause of acute lower respiratory tract infections in high-risk populations, yet there are no vaccines or anti-viral therapies approved for the prevention or treatment of hMPV-associated disease. Here, we used a high-throughput single-cell technology to interrogate memory B cell responses to the hMPV fusion (F) glycoprotein in young adult and elderly donors. Across all donors, the neutralizing antibody response was primarily directed to epitopes expressed on both pre- and post-fusion F conformations. However, we identified rare, highly potent broadly neutralizing antibodies that recognize pre-fusion-specific epitopes and structurally characterized an antibody that targets a site of vulnerability at the pre-fusion F trimer apex. Additionally, monotherapy with neutralizing antibodies targeting three distinct antigenic sites provided robust protection against lower respiratory tract infection in a small animal model. This study provides promising monoclonal antibody candidates for passive immunoprophylaxis and informs the rational design of hMPV vaccine immunogens.

DOI: 10.1016/j.immuni.2022.07.003

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00336-3