A Heterodimeric Antibody Fragment for Passive Immunotherapy Against Norovirus Infection.
Antibodies, Monoclonal
/ administration & dosage
Antibodies, Viral
/ immunology
Caliciviridae Infections
/ immunology
Capsid Proteins
/ genetics
Cross Reactions
Epitopes
/ immunology
Humans
Immunization, Passive
/ methods
Immunoglobulin Fragments
/ administration & dosage
Induced Pluripotent Stem Cells
/ immunology
Norovirus
/ drug effects
Recombinant Proteins
/ immunology
VLP
antibody fragment
norovirus GII.17
norovirus GII.4
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
06 07 2020
06 07 2020
Historique:
received:
27
11
2019
accepted:
21
03
2020
pubmed:
27
3
2020
medline:
17
2
2021
entrez:
27
3
2020
Statut:
ppublish
Résumé
Human noroviruses cause an estimated 685 million infections and 200 000 deaths annually worldwide. Although vaccines against GII.4 and GI.1 genotypes are under development, no information is available regarding vaccines or monoclonal antibodies to other noroviral genotypes. Here, we developed 2 variable-domain llama heavy-chain antibody fragment (VHHs) clones, 7C6 and 1E4, against GII.4 and GII.17 human noroviruses, respectively. Although 7C6 cross-reacted with virus-like particles (VLPs) of GII.17, GII.6, GII.3, and GII.4, it neutralized only GII.4 norovirus. In contrast, 1E4 reacted with and neutralized only GII.17 VLPs. Both VHHs blocked VLP binding to human induced pluripotent stem cell-derived intestinal epithelial cells and carbohydrate attachment factors. Using these 2 VHHs, we produced a heterodimeric VHH fragment that neutralized both GII.4 and GII.17 noroviruses. Because VHH fragments are heat- and acid-stable recombinant monoclonal antibodies, the heterodimer likely will be useful for oral immunotherapy and prophylaxis against GII.4 and GII.17 noroviruses in young, elderly, or immunocompromised persons.
Identifiants
pubmed: 32211769
pii: 5811435
doi: 10.1093/infdis/jiaa115
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Viral
0
Capsid Proteins
0
Epitopes
0
Immunoglobulin Fragments
0
Recombinant Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
470-478Informations de copyright
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.