Profiling of hMPV F-specific antibodies isolated from human memory B cells
Xiao Xiao, Arthur Fridman, Lu Zhang, Pavlo Pristatsky, Eberhard Dürr, Michael Minnier, Aimin Tang, Aimin Tang, Zhiyun Wen, Renée Moore, Dongrui Tian, Jennifer Galli, Scott Cosmi, Michael J. Eddins, Nicole Sullivan, Xiaodong Yan, Andrew J. Bett, H. J. Su, Kalpit A. Vora, Zhifeng Chen, Lan Zhang, Lan Zhang, Lan Zhang
Abstract
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.