A Cross-Reactive Humanized Monoclonal Antibody Targeting Fusion Glycoprotein Function Protects Ferrets Against Lethal Nipah Virus and Hendra Virus Infection

Chad Mire, Yee Peng Chan, Viktoriya Borisevich, Robert W. Cross, Lianying Yan, Krystle N. Agans, Ha V. Dang, David Veesler, Karla Fenton, Thomas W. Geisbert, Christopher C. Broder

Research output: Contribution to journalArticle

Abstract

Background: Nipah virus (NiV) and Hendra virus (HeV) are zoonotic paramyxoviruses that cause severe disease in both animals and humans. There are no approved vaccines or treatments for use in humans; however, therapeutic treatment of both NiV and HeV infection in ferrets and non-human primates with a cross-reactive, neutralizing human monoclonal antibody (mAb), m102.4, targeting the G glycoprotein has been demonstrated. In a previous study, we isolated, characterized, and humanized a cross-reactive, neutralizing anti-F mAb (h5B3.1). The mAb h5B3.1 blocks the required F conformational change needed to facilitate membrane fusion and virus infection, and the epitope recognized by h5B3.1 has been structurally defined; however, the efficacy of h5B3.1 in vivo is unknown. Methods: The post-infection antiviral activity of h5B3.1 was evaluated in vivo by administration in ferrets after NiV and HeV virus challenge. Results: All subjects that received h5B3.1 from 1 to several days after infection with a high-dose, oral-nasal virus challenge were protected from disease, whereas all controls died. Conclusions: This is the first successful post-exposure antibody therapy for NiV and HeV using a humanized cross-reactive mAb targeting the F glycoprotein, and the findings suggest that a combination therapy targeting both F and G should be evaluated as a therapy for NiV/HeV infection.

Original languageEnglish (US)
Pages (from-to)S471-S479
JournalJournal of Infectious Diseases
Volume221
DOIs
StatePublished - May 11 2020

Keywords

  • F glycoprotein
  • Hendra virus
  • Nipah virus
  • membrane fusion
  • monoclonal antibody

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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