Protection against lethal canine distemper virus infection by a dual epitope-targeting synthetic antibody
Despite vaccine availability, the morbilliviruses measles virus and canine distemper virus (CDV) are still causing major health impairments in human and animal populations. Here, we identified two potent, neutralizing single domain antibodies directed against the tetrameric receptor binding (H) protein of CDV. Structural analyses spotlighted two vulnerable sites within the H protein. While the first overlaps with the receptor binding site, the second encompasses amino acid residues of two protomers located at the distal dimeric head interface, which supports distinct mechanisms of neutralization. Upon application of an engineered tetravalent and biparatopic antibody, ferrets were protected at a remarkably low antibody dose (1 mg/kg) administered intra-peritoneally on days 3 and 7 post-exposure of a lethal CDV challenge. Collectively, this study spotlights the power of integrating multiple mechanisms of neutralization in a single format and provides a roadmap to design next-generation therapeutics against morbilliviral infections as well as other infectious pathogens.
Authors
- Oliver Siering
- Christian K. Pfaller (ORCID: https://orcid.org/0000-0003-3302-0780)
- Dimitrios Fotiadis (ORCID: https://orcid.org/0000-0001-9682-7931)
- Patrick Chames
- Rainer Riedl (ORCID: https://orcid.org/0000-0003-2534-1963)
- Melanie Scherer (ORCID: https://orcid.org/0000-0001-5554-9664)
- Nadia Djabeur (ORCID: https://orcid.org/0000-0002-0573-4033)
- Jean-Marc Jeckelmann (ORCID: https://orcid.org/0000-0001-9973-2700)
- Marianne Wyss (ORCID: https://orcid.org/0000-0002-2292-3282)
- Morgane Di Palma Subran
- Bevan Sawatsky
- Philippe Plattet
- Marina Cresci
Institutions
- University of Bern (CH)
- Centre National de la Recherche Scientifique (FR)
- Bern University of Applied Sciences (CH)
- Inserm (FR)
- ZHAW Zurich University of Applied Sciences (CH)
- University of Zurich (CH)
- Aix-Marseille Université (FR)
- Mayo Clinic in Arizona (US)
- Centre de Recherche en Cancérologie de Marseille (FR)
- Mayo Clinic in Florida (US)
- Institut Paoli-Calmettes (FR)
- Paul Ehrlich Institut (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-01-07
- DOI
- https://doi.org/10.1038/s41467-025-67600-z
- Primary Topic
- Virology and Viral Diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- University of Bern
- Deutsche Forschungsgemeinschaft
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung