Human antibodies against West Nile and related orthoflaviviruses
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
- Dragana Mijatović (ORCID: https://orcid.org/0000-0003-4970-0748)
- Benjamin G. Hale (ORCID: https://orcid.org/0000-0002-3891-9480)
- Václav Hönig (ORCID: https://orcid.org/0000-0003-0469-4604)
- Siniša Sević (ORCID: https://orcid.org/0009-0009-3267-1195)
- Zorana Budakov-Obradović
- Jagoda Gavrilović (ORCID: https://orcid.org/0000-0003-3327-3884)
- Jacques Moritz (ORCID: https://orcid.org/0000-0002-2123-360X)
- Jiří Holoubek (ORCID: https://orcid.org/0009-0000-7850-7723)
- Stylianos Bournazos (ORCID: https://orcid.org/0000-0001-5466-5620)
- Margaret R. MacDonald (ORCID: https://orcid.org/0000-0001-5177-2068)
- Davide F. Robbiani (ORCID: https://orcid.org/0000-0001-7379-3484)
- Zaria I. Contejean
- Christopher O. Barnes (ORCID: https://orcid.org/0000-0003-2754-5951)
- Dajana Lendak (ORCID: https://orcid.org/0000-0003-4323-1776)
- Tania Kapoor (ORCID: https://orcid.org/0000-0002-0396-4476)
- Kevin Groen (ORCID: https://orcid.org/0000-0001-6352-1346)
- Zvezdana Lojpur
- Pavle Banović (ORCID: https://orcid.org/0000-0001-7902-6606)
- Simone G. Moro (ORCID: https://orcid.org/0000-0001-5199-8390)
- Monika Bajči
- Luca Simonelli (ORCID: https://orcid.org/0000-0001-6331-7716)
- Martin Palus (ORCID: https://orcid.org/0000-0002-4279-7092)
- Jasmina Grujić (ORCID: https://orcid.org/0000-0003-3092-4768)
- Luca Varani (ORCID: https://orcid.org/0000-0002-0963-0987)
- Tomás Cervantes Rincón (ORCID: https://orcid.org/0000-0002-6355-6781)
- Roger Kuratli (ORCID: https://orcid.org/0009-0004-2917-575X)
- Monika Čížková (ORCID: https://orcid.org/0009-0003-9051-4434)
- Zuzana Krátka (ORCID: https://orcid.org/0000-0003-1134-2084)
- Benedetta Cena
- Jasmine Cantergiani
- Tereza Frčková
- Emily G. Niejadlik
- Roshan Thakur
- David Jarrossay
- Lidija Popovic-Dragonjic
- Marija Vranes
- Filippo Bianchini
- Anna R. E. Robinson
- Jiri Salat
- Daniel Ruzek
- Silvia Tosolini
Institutions
- University of Kragujevac (RS)
- University of Nis (RS)
- University of Novi Sad (RS)
- University of Zurich (CH)
- Masaryk University (CZ)
- Klinički centar Vojvodine (RS)
- University of South Bohemia in České Budějovice (CZ)
- Veterinary Research Institute (CZ)
- Chan Zuckerberg Initiative (United States) (US)
- Stanford Medicine (US)
- Clinical Centre of Kragujevac (RS)
- Institute of Parasitology (CZ)
- Czech Academy of Sciences, Biology Centre (CZ)
- Università della Svizzera italiana (CH)
- Rockefeller University (US)
- Stanford University (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-04-06
- DOI
- https://doi.org/10.64898/2026.04.02.715800
- Primary Topic
- Mosquito-borne diseases and control
- Type
- article
- Field-Weighted Citation Impact
- 0.00
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