A monoclonal antibody targeting the Nipah virus fusion glycoprotein apex imparts protection from disease

DOI: 10.1128/jvi.00638-24

Authors: Victoria A. Avanzato (National Institutes of Health; Wellcome Centre for Human Genetics, University of Oxford) , Trenton Bushmaker (National Institute of Allergy and Infectious Diseases, National Institutes of Health) , Kasopefoluwa Y. Oguntuyo (Icahn School of Medicine at Mount Sinai) , Claude Kwe Yinda (National Institutes of Health) , Helen M. E. Duyvesteyn (Wellcome Centre for Human Genetics, University of Oxford) , Robert Stass (Wellcome Centre for Human Genetics, University of Oxford) , Kimberly Meade-White (National Institute of Allergy and Infectious Diseases, National Institutes of Health) , Rebecca Rosenke (National Institute of Allergy and Infectious Diseases, National Institutes of Health) , Tina Thomas (National Institute of Allergy and Infectious Diseases, National Institutes of Health) , Neeltje Van Doremalen (National Institute of Allergy and Infectious Diseases, National Institutes of Health) , Greg Saturday (National Institute of Allergy and Infectious Diseases, National Institutes of Health) , Katie J. Doores (King's College London) , Benhur Lee (Icahn School of Medicine at Mount Sinai) , Thomas A. Bowden (Wellcome Centre for Human Genetics, University of Oxford) , Vincent J. Munster (National Institute of Allergy and Infectious Diseases, National Institutes of Health)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Virology

State: Published (Approved)
Published: September 2024
Diamond Proposal Number(s): 20223

Abstract: Nipah virus (NiV) is a highly pathogenic paramyxovirus capable of causing severe respiratory and neurologic disease in humans. Currently, there are no licensed vaccines or therapeutics against NiV, underscoring the urgent need for the development of countermeasures. The NiV surface-displayed glycoproteins, NiV-G and NiV-F, mediate host cell attachment and fusion, respectively, and are heavily targeted by host antibodies. Here, we describe a vaccination-derived neutralizing monoclonal antibody, mAb92, that targets NiV-F. Structural characterization of the Fab region bound to NiV-F (NiV-F–Fab92) by cryo-electron microscopy analysis reveals an epitope in the DIII domain at the membrane distal apex of NiV-F, an established site of vulnerability on the NiV surface. Further, prophylactic treatment of hamsters with mAb92 offered complete protection from NiV disease, demonstrating beneficial activity of mAb92 in vivo. This work provides support for targeting NiV-F in the development of vaccines and therapeutics against NiV.

Diamond Keywords: Nipah Virus (NiV); Viruses

Subject Areas: Biology and Bio-materials, Medicine

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios I-Titan Krios I at Diamond

Added On: 11/09/2024 13:47

Discipline Tags:

Vaccines Pathogens Infectious Diseases Health & Wellbeing Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Microscopy Electron Microscopy (EM) Cryo Electron Microscopy (Cryo EM)