SUMMARY/ABSTRACT
Nipah virus (NiV) is a pathogenic paramyxovirus that causes fatal encephalitis in humans. Two envelope glycoproteins, the attachment protein (G) and fusion protein (F), facilitate entry into host cells. Due to its vital role, NiV F presents an attractive target for developing vaccines and therapeutics. Several neutralization-sensitive epitopes on the NiV F apex have been described, however the antigenicity of most of the F protein’s surface remains uncharacterized. Here, we immunize mice with prefusion-stabilized NiV F and isolate ten monoclonal antibodies that neutralize pseudotyped virus. Cryo-electron microscopy reveals eight neutralization-sensitive epitopes on NiV F, four of which have not previously been described. Novel sites span the lateral and basal faces of NiV F, expanding the known library of vulnerable epitopes. This work identifies new epitopes as targets for therapeutics, provides a molecular basis for NiV neutralization, and lays a foundation for development of new antibodies targeting NiV F.
Competing Interest Statement
YT is employed by Leidos Biomedical Research, Inc., supported in part with funds from the Frederick National Laboratory for Cancer Research, NIH, under contract HHSN261200800001. BSG and RJL are inventors on patent application #63315934, filed March 2, 2022, entitled "Monoclonal Antibodies to Nipah Virus F Protein and Their Use". This patent describes the 10 neutralizing antibodies in this manuscript.