Human antibodies against West Nile and related orthoflaviviruses
Year: 2026
Type: preprint
Abstract: West Nile virus (WNV) is a mosquito-borne pathogen of global concern that can cause fatal neuroinvasive disease. No specific prophylaxis or treatment exists for WNV or related orthoflavivirus infections, and the determinants of human disease severity remain poorly understood. Here, we report that neutralizing autoantibodies against type I interferons do not impair antiviral antibody development. Among the fully human monoclonal antibodies with potent neutralizing activity against WNV that were discovered, W010 targets a unique epitope within the envelope protein domain III (EDIII) and confers both pre- and post-exposure protection in a murine WNV model, even when interferon signaling is impaired. A second protective antibody, W014, exhibits broad cross-neutralization of other pathogenic orthoflavivirus members, including Japanese encephalitis virus, Murray Valley encephalitis virus, Saint Louis encephalitis virus, and Usutu virus. These findings identify key neutralizing epitopes on WNV EDIII and provide candidates for the development of antibody-based interventions against encephalitic orthoflavivirus infections.
Authors: Tomás Cervantes Rincón, Tereza Frckova, Zaria I. Contejean, Jasmine Cantergiani, Kevin Groen, Benedetta Cena, Simone G. Moro, Filippo Bianchini, Luca Simonelli, David Jarrossay, Silvia Tosolini, Roger Kuratli, Anna R. E. Robinson, Monika Cizkova, Emily G. Niejadlik, Jacques Moritz, Roshan Thakur, Zuzana Krátka, Dragana Mijatović, Jasmina Grujić, Jiri Holoubek, Zorana Budakov-Obradović, Jiri Salat, Václav Hönig, Marija Vraneš, Zvezdana Lojpur, Dajana Lendak, Siniša Sević, Monika Bajči, Lidija Popović-Dragonjić, Biljana Popovska Jovicic, Jagoda Gavrilovic, Tania Kapoor, Margaret R. MacDonald, Stylianos Bournazos, Luca Varani, Martin Palus, Benjamin G. Hale, Pavle Banović, Daniel Ruzek, Christopher O. Barnes, Davide F. Robbiani
Institutions: Institute for Research in Biomedicine, Università della Svizzera italiana, Masaryk University, Veterinary Research Institute, Stanford Medicine, Stanford University, University of Zurich, University of South Bohemia in České Budějovice, Institute of Parasitology, Czech Academy of Sciences, Biology Centre, Rockefeller University, University of Novi Sad, University of Kragujevac, Clinical Centre of Kragujevac, Klinički centar Vojvodine, University of Nis, Chan Zuckerberg Biohub San Francisco
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: National Science Foundation, Rita Allen Foundation, European Commission, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Grantová Agentura České Republiky, Akademie Věd České Republiky, Swiss Vaccine Research Institute, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
Awards: The human immune response to West Nile virus infection, Counter-acting the pandemic potential of flaviviruses: addressing virus-host interactions and defense strategies to design new therapeutics against WNV and DENV, G2133649503, G2677629327, G2678520069, G3011267836, G3491845953, G3810236772, G3818306261, European Virus Archive GLOBAL, G4396925471, G532636064, Human antibodies to flavivirus threats, Integrating innate and adaptive pathways in vaccine responses, Epitope-focused vaccine strategies against Zika virus, G7931965296, Multispecific antibodies against infectious diseases, G9000007701, G9000049533, G9000064110, G9000076339, G9000115855, G9000264621, G9000346859, A Synchrotron Radiation Structural Biology Resource, SARS-CoV-2: understanding the entry, multi-organ spread, and immune response in the context of vaccination and re-infection
OpenAlex ID: W7150914193