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

• Published in: The Journal of infectious diseases Vol. 221; no. Supplement_4; pp. S471 - S479
• Main Authors: Mire, Chad E, Chan, Yee-Peng, Borisevich, Viktoriya, Cross, Robert W, Yan, Lianying, Agans, Krystle N, Dang, Ha V, Veesler, David, Fenton, Karla A, Geisbert, Thomas W, Broder, Christopher C
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 11-05-2020
• Subjects: Animals; Antibodies; Antibodies, Monoclonal - therapeutic use; Antiviral activity; Antiviral drugs; Cross Reactions; Epitopes; Ferrets; Glycoproteins; Hendra Virus; Henipavirus Infections - prevention & control; Henipavirus Infections - therapy; Henipavirus Infections - virology; Humans; Immunotherapy; Infections; Membrane fusion; Monoclonal antibodies; Mustela; Nipah Virus; Supplement; Viral Fusion Proteins - immunology; Zoonoses; F glycoprotein; Nipah virus; monoclonal antibody; Hendra virus; membrane fusion
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiz515

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.