A Cross-Reactive Humanized Monoclonal Antibody Targeting Fusion Glycoprotein Function Protects Ferrets Against Lethal Nipah Virus and Hendra Virus Infection.
Chad E Mire, Yee-Peng Chan, Viktoriya Borisevich, Robert W Cross, Lianying Yan, Krystle N Agans, Ha V Dang, David Veesler, Karla A Fenton, Thomas W Geisbert, Christopher C Broder
Author Information
Chad E Mire: Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA.
Yee-Peng Chan: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Viktoriya Borisevich: Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA.
Robert W Cross: Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA.
Lianying Yan: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Krystle N Agans: Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA.
Ha V Dang: Department of Biochemistry, University of Washington, Seattle, Washington, USA.
David Veesler: Department of Biochemistry, University of Washington, Seattle, Washington, USA.
Karla A Fenton: Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA.
Thomas W Geisbert: Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA.
Christopher C Broder: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
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.
