Single low-dose VSV-EBOV vaccination protects cynomolgus macaques from lethal Ebola challenge
Summary: 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 clin...
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Elsevier
2019-11-01
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Series: | EBioMedicine |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419306516 |
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record_format |
Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Andrea Marzi Pierce Reynolds Reinaldo Mercado-Hernandez Julie Callison Friederike Feldmann Rebecca Rosenke Tina Thomas Dana P. Scott Patrick W. Hanley Elaine Haddock Heinz Feldmann |
spellingShingle |
Andrea Marzi Pierce Reynolds Reinaldo Mercado-Hernandez Julie Callison Friederike Feldmann Rebecca Rosenke Tina Thomas Dana P. Scott Patrick W. Hanley Elaine Haddock Heinz Feldmann Single low-dose VSV-EBOV vaccination protects cynomolgus macaques from lethal Ebola challenge EBioMedicine |
author_facet |
Andrea Marzi Pierce Reynolds Reinaldo Mercado-Hernandez Julie Callison Friederike Feldmann Rebecca Rosenke Tina Thomas Dana P. Scott Patrick W. Hanley Elaine Haddock Heinz Feldmann |
author_sort |
Andrea Marzi |
title |
Single low-dose VSV-EBOV vaccination protects cynomolgus macaques from lethal Ebola challenge |
title_short |
Single low-dose VSV-EBOV vaccination protects cynomolgus macaques from lethal Ebola challenge |
title_full |
Single low-dose VSV-EBOV vaccination protects cynomolgus macaques from lethal Ebola challenge |
title_fullStr |
Single low-dose VSV-EBOV vaccination protects cynomolgus macaques from lethal Ebola challenge |
title_full_unstemmed |
Single low-dose VSV-EBOV vaccination protects cynomolgus macaques from lethal Ebola challenge |
title_sort |
single low-dose vsv-ebov vaccination protects cynomolgus macaques from lethal ebola challenge |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2019-11-01 |
description |
Summary: 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: 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: We observed complete protection from disease with VSV-EBOV doses ranging from 1 × 107 to 1 × 101 plaque-forming units. Some protected animals receiving lower vaccine doses developed temporary low-level EBOV viremia. Control animals developed classical EBOV disease and reached euthanasia criteria within a week after challenge. This study demonstrates that very low doses of VSV-EBOV uniformly protect macaques against lethal EBOV challenge. Interpretation: 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: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Keywords: Ebola virus, EBOV-Makona, Macaque model, VSV-EBOV, Low-dose vaccination |
url |
http://www.sciencedirect.com/science/article/pii/S2352396419306516 |
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doaj-d2ab3b2c1f4b4911a5be3ba1b2a083cb2020-11-25T01:15:03ZengElsevierEBioMedicine2352-39642019-11-0149223231Single low-dose VSV-EBOV vaccination protects cynomolgus macaques from lethal Ebola challengeAndrea Marzi0Pierce Reynolds1Reinaldo Mercado-Hernandez2Julie Callison3Friederike Feldmann4Rebecca Rosenke5Tina Thomas6Dana P. Scott7Patrick W. Hanley8Elaine Haddock9Heinz Feldmann10Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA; Corresponding authors at: Laboratory of Virology, Rocky Mountain Laboratories, 903 South 4th Street, Hamilton, MT 59840, USA.Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USALaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USALaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USARocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USARocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USALaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USARocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USARocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USALaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USALaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA; Corresponding authors at: Laboratory of Virology, Rocky Mountain Laboratories, 903 South 4th Street, Hamilton, MT 59840, USA.Summary: 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: 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: We observed complete protection from disease with VSV-EBOV doses ranging from 1 × 107 to 1 × 101 plaque-forming units. Some protected animals receiving lower vaccine doses developed temporary low-level EBOV viremia. Control animals developed classical EBOV disease and reached euthanasia criteria within a week after challenge. This study demonstrates that very low doses of VSV-EBOV uniformly protect macaques against lethal EBOV challenge. Interpretation: 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: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Keywords: Ebola virus, EBOV-Makona, Macaque model, VSV-EBOV, Low-dose vaccinationhttp://www.sciencedirect.com/science/article/pii/S2352396419306516 |