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

Nat Struct Mol Biol. 2021 May;28(5):426-434. doi: 10.1038/s41594-021-00584-8. Epub 2021 Apr 29.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / immunology
  • Antibodies, Viral / immunology*
  • Broadly Neutralizing Antibodies / immunology*
  • CHO Cells
  • Cricetulus
  • Cross Reactions
  • HEK293 Cells
  • Hendra Virus / immunology*
  • Henipavirus Infections / immunology
  • Henipavirus Infections / prevention & control
  • Humans
  • Mice
  • Nipah Virus / immunology*
  • Viral Fusion Proteins / immunology*
  • Virus Internalization

Substances

  • Antibodies, Monoclonal, Humanized
  • Antibodies, Viral
  • Broadly Neutralizing Antibodies
  • Viral Fusion Proteins