Title : Characterization of prefusion-F-specific antibodies elicited by natural infection with human metapneumovirus from two older adults
Abstract:
Human metapneumovirus (hMPV) is a major cause of acute respiratory tract infections in both infants and older adults. Currently there are no approved vaccines or antibody therapies for treatment against infection from hMPV. The key target of neutralizing antibodies is the viral fusion (F) glycoprotein, which is required for viral entry. However, little is known about the humoral immune response elicited by humans after natural infection with hMPV. In this study, we used stabilized hMPV F protein trimers to isolate and sort hMPV F-specific B cells from two older adults. We obtained hundreds of class-switched antibody sequences representing over 500 clonotypes, indicative of a highly polyclonal antibody response to hMPV F in these two individuals. In-depth characterization of 136 of these monoclonal antibodies revealed broad recognition of the hMPV F surface, with potent neutralizing antibodies targeting several distinct antigenic sites. Cryo-EM structures were solved for two of the neutralizing antibodies in complex with hMPV F, revealing the molecular basis for recognition of two prefusion-specific epitopes at the apex of the F trimer. These results provide new insights into the humoral response to hMPV infection in older adults and can help guide development of novel vaccine immunogens.
Audience Take Away:
- How hMPV F-specific antibodies from human PBMC were isolated
- Characteristics of antibodies to distinct epitopes on the surface of hMPV F trimer
Information that could be used for improved hMPV F immunogen design
