Abstract
Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness with fatality rates of 50–100%. No vaccines or licensed therapeutics currently exist to protect humans against NiV or HeV. HNVs enter host cells by fusing the viral and cellular membranes via the concerted action of the attachment (G) and fusion (F) glycoproteins, the main targets of the humoral immune response. Here, we describe the isolation and humanization of a potent monoclonal antibody cross-neutralizing NiV and HeV. Cryo-electron microscopy, triggering and fusion studies show the antibody binds to a prefusion-specific quaternary epitope, conserved in NiV F and HeV F glycoproteins, and prevents membrane fusion and viral entry. This work supports the importance of the HNV prefusion F conformation for eliciting a robust immune response and paves the way for using this antibody for prophylaxis and post-exposure therapy with NiV- and HeV-infected individuals.
| Original language | English |
|---|---|
| Pages (from-to) | 980-987 |
| Number of pages | 8 |
| Journal | Nature Structural and Molecular Biology |
| Volume | 26 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 1 Oct 2019 |
| Externally published | Yes |
Funding
We thank M.M. Sauer for his assistance with biolayer interferometry assays and N. Zheng for providing access to his crystallization robot. This study was supported by the National Institute of Allergy and Infectious Diseases (D.V., HHSN272201700059C; C.C.B., AI054715, AI077995 and AI142764), the National Institute of General Medical Sciences (D.V., GM120553), an Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund (D.V.), a Pew Biomedical Scholars Award (D.V.), the Netherlands Organization for Scientific Research (J.S., Rubicon 019.2015.2.310.006), the European Molecular Biology Organisation (J.S., ALTF933-2015), the University of Washington Arnold and Mabel Beckman cryo-EM center and Proteomics Resource (UWPR95794) and Beamline 5.0.1 at the Advanced Light Source at Lawrence Berkley National Laboratory, which is a Department of Energy Office of Science User Facility under contract no. DE-AC02-05CH11231 and is supported by the Howard Hughes Medical Institute and NIH grant no. S10OD021832.
