Development of safe and highly protective live-attenuated SARS-CoV-2 vaccine candidates by genome recoding.
COVID-19
Roborovski dwarf hamster
SARS-CoV-2
Syrian hamster
codon pair deoptimization
coronavirus
genome recoding
live attenuated vaccine
synthetic attenuated virus engineering
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
03 08 2021
03 08 2021
Historique:
received:
20
01
2021
revised:
21
05
2021
accepted:
14
07
2021
pubmed:
29
7
2021
medline:
14
8
2021
entrez:
28
7
2021
Statut:
ppublish
Résumé
Safe and effective vaccines are urgently needed to stop the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We construct a series of live attenuated vaccine candidates by large-scale recoding of the SARS-CoV-2 genome and assess their safety and efficacy in Syrian hamsters. Animals were vaccinated with a single dose of the respective recoded virus and challenged 21 days later. Two of the tested viruses do not cause clinical symptoms but are highly immunogenic and induce strong protective immunity. Attenuated viruses replicate efficiently in the upper but not in the lower airways, causing only mild pulmonary histopathology. After challenge, hamsters develop no signs of disease and rapidly clear challenge virus: at no time could infectious virus be recovered from the lungs of infected animals. The ease with which attenuated virus candidates can be produced and administered favors their further development as vaccines to combat the ongoing pandemic.
Identifiants
pubmed: 34320400
pii: S2211-1247(21)00920-7
doi: 10.1016/j.celrep.2021.109493
pmc: PMC8289629
pii:
doi:
Substances chimiques
COVID-19 Vaccines
0
Vaccines, Attenuated
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
109493Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests Freie Universität Berlin and the University of Bern received funding from a commercial partner for research similar to that described in this manuscript.
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