Single low-dose VSV-EBOV vaccination protects cynomolgus macaques from lethal Ebola challenge.
EBOV-Makona
Ebola virus
Low-dose vaccination
Macaque model
VSV-EBOV
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Nov 2019
Nov 2019
Historique:
received:
08
08
2019
revised:
19
09
2019
accepted:
25
09
2019
pubmed:
22
10
2019
medline:
1
4
2020
entrez:
22
10
2019
Statut:
ppublish
Résumé
Ebola virus (EBOV), variant Makona, was the causative agent of the 2013-2016 West African epidemic responsible for almost 30,000 human infections and over 11,000 fatalities. During the epidemic, the development of several experimental vaccines was accelerated through human clinical trials. One of them, the vesicular stomatitis virus (VSV)-based vaccine VSV-EBOV, showed promising efficacy in a phase 3 clinical trial in Guinea and is currently used in the ongoing EBOV outbreak in the northeastern part of the Democratic Republic of the Congo (DRC). This vaccine expresses the EBOV-Kikwit glycoprotein from the 1995 outbreak as the immunogen. Here we generated a VSV-based vaccine expressing the contemporary EBOV-Makona glycoprotein. We characterized the vaccine in tissue culture and analyzed vaccine efficacy in the cynomolgus macaque model. Subsequently, we determined the dose-dependent protective efficacy in nonhuman primates against lethal EBOV challenge. We observed complete protection from disease with VSV-EBOV doses ranging from 1 × 10 Our study provides missing pre-clinical data supporting the use of reduced VSV-EBOV vaccine doses without decreasing protective efficacy and at the same time increase vaccine safety and availability - two critical concerns in public health response. Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.
Sections du résumé
BACKGROUND
BACKGROUND
Ebola virus (EBOV), variant Makona, was the causative agent of the 2013-2016 West African epidemic responsible for almost 30,000 human infections and over 11,000 fatalities. During the epidemic, the development of several experimental vaccines was accelerated through human clinical trials. One of them, the vesicular stomatitis virus (VSV)-based vaccine VSV-EBOV, showed promising efficacy in a phase 3 clinical trial in Guinea and is currently used in the ongoing EBOV outbreak in the northeastern part of the Democratic Republic of the Congo (DRC). This vaccine expresses the EBOV-Kikwit glycoprotein from the 1995 outbreak as the immunogen.
METHODS
METHODS
Here we generated a VSV-based vaccine expressing the contemporary EBOV-Makona glycoprotein. We characterized the vaccine in tissue culture and analyzed vaccine efficacy in the cynomolgus macaque model. Subsequently, we determined the dose-dependent protective efficacy in nonhuman primates against lethal EBOV challenge.
FINDINGS
RESULTS
We observed complete protection from disease with VSV-EBOV doses ranging from 1 × 10
INTERPRETATION
CONCLUSIONS
Our study provides missing pre-clinical data supporting the use of reduced VSV-EBOV vaccine doses without decreasing protective efficacy and at the same time increase vaccine safety and availability - two critical concerns in public health response.
FUNDING
BACKGROUND
Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.
Identifiants
pubmed: 31631035
pii: S2352-3964(19)30651-6
doi: 10.1016/j.ebiom.2019.09.055
pmc: PMC6945200
pii:
doi:
Substances chimiques
Cytokines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
223-231Informations de copyright
Published by Elsevier B.V.
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