Multimeric single-domain antibody complexes protect against bunyavirus infections.
bunyavirus
infectious disease
microbiology
rift valley fever virus
schmallenberg virus
single-domain antibody
therapy
vhh
virus
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
21 04 2020
21 04 2020
Historique:
received:
14
10
2019
accepted:
11
04
2020
entrez:
22
4
2020
pubmed:
22
4
2020
medline:
1
4
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32314955
doi: 10.7554/eLife.52716
pii: 52716
pmc: PMC7173960
doi:
pii:
Substances chimiques
Antibodies, Neutralizing
0
Antiviral Agents
0
Single-Domain Antibodies
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Innovative Medicines Initiative
ID : ZAPI (grant agreement no. 115760)
Organisme : Ministerio de Ciencia Tecnología y Telecomunicaciones
ID : Student Fellowship (PEM-066-2015-II)
Organisme : Universidad de Costa Rica
ID : Student Fellowship (OAICE-CAB-05-56-2016)
Informations de copyright
© 2020, Wichgers Schreur et al.
Déclaration de conflit d'intérêts
PW, Sv, MH, EB, DD, FG, KW, MB, AA, JH, PG, FR, Lv, JK No competing interests declared, OD, SR, KB, DK, MS, KM, ZD is an employee of AstraZeneca.
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