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© Research
Publication : eLife

Multimeric single-domain antibody complexes protect against bunyavirus infections.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in eLife - 21 Apr 2020

Wichgers Schreur PJ, van de Water S, Harmsen M, Bermúdez-Méndez E, Drabek D, Grosveld F, Wernike K, Beer M, Aebischer A, Daramola O, Rodriguez Conde S, Brennan K, Kozub D, Søndergaard Kristiansen M, Mistry KK, Deng Z, Hellert J, Guardado-Calvo P, Rey FA, van Keulen L, Kortekaas J,

Link to Pubmed [PMID] – 32314955

Link to DOI – e5271610.7554/eLife.52716

Elife 2020 Apr; 9():

The World Health Organization has included three bunyaviruses posing an increasing threat to human health on the Blueprint list of viruses likely to cause major epidemics and for which no, or insufficient countermeasures exist. Here, we describe a broadly applicable strategy, based on llama-derived single-domain antibodies (VHHs), for the development of bunyavirus biotherapeutics. The method was validated using the zoonotic Rift Valley fever virus (RVFV) and Schmallenberg virus (SBV), an emerging pathogen of ruminants, as model pathogens. VHH building blocks were assembled into highly potent neutralizing complexes using bacterial superglue technology. The multimeric complexes were shown to reduce and prevent virus-induced morbidity and mortality in mice upon prophylactic administration. Bispecific molecules engineered to present two different VHHs fused to an Fc domain were further shown to be effective upon therapeutic administration. The presented VHH-based technology holds great promise for the development of bunyavirus antiviral therapies.