Broadly neutralizing antibody cocktails targeting Nipah virus and Hendra virus fusion glycoproteins

Ha V. Dang, Robert W. Cross, Viktoriya Borisevich, Zachary A. Bornholdt, Brandyn R. West, Yee Peng Chan, Chad E. Mire, Sofia Cheliout Da Silva, Antony S. Dimitrov, Lianying Yan, Moushimi Amaya, Chanakha K. Navaratnarajah, Larry Zeitlin, Thomas W. Geisbert, Christopher C. Broder, David Veesler

Research output: Contribution to journalArticlepeer-review

Abstract

Hendra virus (HeV) and Nipah virus (NiV) are henipaviruses (HNVs) causing respiratory illness and severe encephalitis in humans, with fatality rates of 50–100%. There are no licensed therapeutics or vaccines to protect humans. HeV and NiV use a receptor-binding glycoprotein (G) and a fusion glycoprotein (F) to enter host cells. HNV F and G are the main targets of the humoral immune response, and the presence of neutralizing antibodies is a correlate of protection against NiV and HeV in experimentally infected animals. We describe here two cross-reactive F-specific antibodies, 1F5 and 12B2, that neutralize NiV and HeV through inhibition of membrane fusion. Cryo-electron microscopy structures reveal that 1F5 and 12B2 recognize distinct prefusion-specific, conserved quaternary epitopes and lock F in its prefusion conformation. We provide proof-of-concept for using antibody cocktails for neutralizing NiV and HeV and define a roadmap for developing effective countermeasures against these highly pathogenic viruses.

Original languageEnglish (US)
Pages (from-to)426-434
Number of pages9
JournalNature Structural and Molecular Biology
Volume28
Issue number5
DOIs
StatePublished - May 2021

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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