A non-transmissible live attenuated SARS-CoV-2 vaccine.
COVID-19
SARS-CoV-2
live attenuated virus
mucosal vaccination
pneumonia
vaccine
virus transmission
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581
Informations de publication
Date de publication:
02 08 2023
02 08 2023
Historique:
received:
04
10
2022
revised:
23
03
2023
accepted:
05
05
2023
medline:
7
8
2023
pubmed:
2
6
2023
entrez:
1
6
2023
Statut:
ppublish
Résumé
Live attenuated vaccines (LAVs) administered via the mucosal route may offer better control of the COVID-19 pandemic than non-replicating vaccines injected intramuscularly. Conceptionally, LAVs have several advantages, including presentation of the entire antigenic repertoire of the virus, and the induction of strong mucosal immunity. Thus, immunity induced by LAV could offer superior protection against future surges of COVID-19 cases caused by emerging SARS-CoV-2 variants. However, LAVs carry the risk of unintentional transmission. To address this issue, we investigated whether transmission of a SARS-CoV-2 LAV candidate can be blocked by removing the furin cleavage site (FCS) from the spike protein. The level of protection and immunity induced by the attenuated virus with the intact FCS was virtually identical to the one induced by the attenuated virus lacking the FCS. Most importantly, removal of the FCS completely abolished horizontal transmission of vaccine virus between cohoused hamsters. Furthermore, the vaccine was safe in immunosuppressed animals and showed no tendency to recombine in vitro or in vivo with a SARS-CoV-2 field strain. These results indicate that removal of the FCS from SARS-CoV-2 LAV is a promising strategy to increase vaccine safety and prevent vaccine transmission without compromising vaccine efficacy.
Identifiants
pubmed: 37263272
pii: S1525-0016(23)00260-5
doi: 10.1016/j.ymthe.2023.05.004
pmc: PMC10214529
pii:
doi:
Substances chimiques
COVID-19 Vaccines
0
Vaccines, Attenuated
0
Antibodies, Viral
0
Antibodies, Neutralizing
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2391-2407Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests Related to this work, Freie Universität Berlin has filed a patent application for the use of sCPD9 and sCPD9-ΔFCS as vaccine. In this application, J.T., N.O., and D.K. are named as inventors of sCPD9. Freie Universität Berlin is collaborating with RocketVax AG for further development of sCPD9-ΔFCS as vaccine and receives funding for research.
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