Integrated pipeline for the accelerated discovery of antiviral antibody therapeutics.
Journal
Nature biomedical engineering
ISSN: 2157-846X
Titre abrégé: Nat Biomed Eng
Pays: England
ID NLM: 101696896
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
09
03
2020
accepted:
26
06
2020
pubmed:
5
8
2020
medline:
30
1
2021
entrez:
5
8
2020
Statut:
ppublish
Résumé
The emergence and re-emergence of highly virulent viral pathogens with the potential to cause a pandemic creates an urgent need for the accelerated discovery of antiviral therapeutics. Antiviral human monoclonal antibodies (mAbs) are promising candidates for the prevention and treatment of severe viral diseases, but their long development timeframes limit their rapid deployment and use. Here, we report the development of an integrated sequence of technologies, including single-cell mRNA-sequence analysis, bioinformatics, synthetic biology and high-throughput functional analysis, that enables the rapid discovery of highly potent antiviral human mAbs, the activity of which we validated in vivo. In a 78-d study modelling the deployment of a rapid response to an outbreak, we isolated more than 100 human mAbs that are specific to Zika virus, assessed their function, identified that 29 of these mAbs have broadly neutralizing activity, and verified the therapeutic potency of the lead candidates in mice and non-human primate models of infection through the delivery of an antibody-encoding mRNA formulation and of the respective IgG antibody. The pipeline provides a roadmap for rapid antibody-discovery programmes against viral pathogens of global concern.
Identifiants
pubmed: 32747832
doi: 10.1038/s41551-020-0594-x
pii: 10.1038/s41551-020-0594-x
pmc: PMC7655621
mid: NIHMS1607605
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Viral
0
Antiviral Agents
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1030-1043Subventions
Organisme : NIAID NIH HHS
ID : 75N93019C00074
Pays : United States
Organisme : NLM NIH HHS
ID : T15 LM007450
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI127828
Pays : United States
Organisme : NIH HHS
ID : S10 OD021737
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201400058C
Pays : United States
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