Homologous and heterologous protection of nonhuman primates by Ebola and Sudan virus-like particles.

Filoviruses cause hemorrhagic fever resulting in significant morbidity and mortality in humans. Several vaccine platforms that include multiple virus-vectored approaches and virus-like particles (VLPs) have shown efficacy in nonhuman primates. Previous studies have shown protection of cynomolgus mac...

Full description

Bibliographic Details
Main Authors: Kelly L Warfield, John M Dye, Jay B Wells, Robert C Unfer, Frederick W Holtsberg, Sergey Shulenin, Hong Vu, Dana L Swenson, Sina Bavari, M Javad Aman
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0118881
_version_ 1818835334883966976
author Kelly L Warfield
John M Dye
Jay B Wells
Robert C Unfer
Frederick W Holtsberg
Sergey Shulenin
Hong Vu
Dana L Swenson
Sina Bavari
M Javad Aman
author_facet Kelly L Warfield
John M Dye
Jay B Wells
Robert C Unfer
Frederick W Holtsberg
Sergey Shulenin
Hong Vu
Dana L Swenson
Sina Bavari
M Javad Aman
author_sort Kelly L Warfield
collection DOAJ
description Filoviruses cause hemorrhagic fever resulting in significant morbidity and mortality in humans. Several vaccine platforms that include multiple virus-vectored approaches and virus-like particles (VLPs) have shown efficacy in nonhuman primates. Previous studies have shown protection of cynomolgus macaques against homologous infection for Ebola virus (EBOV) and Marburg virus (MARV) following a three-dose vaccine regimen of EBOV or MARV VLPs, as well as heterologous protection against Ravn Virus (RAVV) following vaccination with MARV VLPs. The objectives of the current studies were to determine the minimum number of vaccine doses required for protection (using EBOV as the test system) and then demonstrate protection against Sudan virus (SUDV) and Taï Forest virus (TAFV). Using the EBOV nonhuman primate model, we show that one or two doses of VLP vaccine can confer protection from lethal infection. VLPs containing the SUDV glycoprotein, nucleoprotein and VP40 matrix protein provide complete protection against lethal SUDV infection in macaques. Finally, we demonstrate protective efficacy mediated by EBOV, but not SUDV, VLPs against TAFV; this is the first demonstration of complete cross-filovirus protection using a single component heterologous vaccine within the Ebolavirus genus. Along with our previous results, this observation provides strong evidence that it will be possible to develop and administer a broad-spectrum VLP-based vaccine that will protect against multiple filoviruses by combining only three EBOV, SUDV and MARV components.
first_indexed 2024-12-19T02:49:04Z
format Article
id doaj.art-4be6a58712434a6db06a646cdaa6bcab
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-19T02:49:04Z
publishDate 2015-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-4be6a58712434a6db06a646cdaa6bcab2022-12-21T20:38:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01103e011888110.1371/journal.pone.0118881Homologous and heterologous protection of nonhuman primates by Ebola and Sudan virus-like particles.Kelly L WarfieldJohn M DyeJay B WellsRobert C UnferFrederick W HoltsbergSergey ShuleninHong VuDana L SwensonSina BavariM Javad AmanFiloviruses cause hemorrhagic fever resulting in significant morbidity and mortality in humans. Several vaccine platforms that include multiple virus-vectored approaches and virus-like particles (VLPs) have shown efficacy in nonhuman primates. Previous studies have shown protection of cynomolgus macaques against homologous infection for Ebola virus (EBOV) and Marburg virus (MARV) following a three-dose vaccine regimen of EBOV or MARV VLPs, as well as heterologous protection against Ravn Virus (RAVV) following vaccination with MARV VLPs. The objectives of the current studies were to determine the minimum number of vaccine doses required for protection (using EBOV as the test system) and then demonstrate protection against Sudan virus (SUDV) and Taï Forest virus (TAFV). Using the EBOV nonhuman primate model, we show that one or two doses of VLP vaccine can confer protection from lethal infection. VLPs containing the SUDV glycoprotein, nucleoprotein and VP40 matrix protein provide complete protection against lethal SUDV infection in macaques. Finally, we demonstrate protective efficacy mediated by EBOV, but not SUDV, VLPs against TAFV; this is the first demonstration of complete cross-filovirus protection using a single component heterologous vaccine within the Ebolavirus genus. Along with our previous results, this observation provides strong evidence that it will be possible to develop and administer a broad-spectrum VLP-based vaccine that will protect against multiple filoviruses by combining only three EBOV, SUDV and MARV components.https://doi.org/10.1371/journal.pone.0118881
spellingShingle Kelly L Warfield
John M Dye
Jay B Wells
Robert C Unfer
Frederick W Holtsberg
Sergey Shulenin
Hong Vu
Dana L Swenson
Sina Bavari
M Javad Aman
Homologous and heterologous protection of nonhuman primates by Ebola and Sudan virus-like particles.
PLoS ONE
title Homologous and heterologous protection of nonhuman primates by Ebola and Sudan virus-like particles.
title_full Homologous and heterologous protection of nonhuman primates by Ebola and Sudan virus-like particles.
title_fullStr Homologous and heterologous protection of nonhuman primates by Ebola and Sudan virus-like particles.
title_full_unstemmed Homologous and heterologous protection of nonhuman primates by Ebola and Sudan virus-like particles.
title_short Homologous and heterologous protection of nonhuman primates by Ebola and Sudan virus-like particles.
title_sort homologous and heterologous protection of nonhuman primates by ebola and sudan virus like particles
url https://doi.org/10.1371/journal.pone.0118881
work_keys_str_mv AT kellylwarfield homologousandheterologousprotectionofnonhumanprimatesbyebolaandsudanviruslikeparticles
AT johnmdye homologousandheterologousprotectionofnonhumanprimatesbyebolaandsudanviruslikeparticles
AT jaybwells homologousandheterologousprotectionofnonhumanprimatesbyebolaandsudanviruslikeparticles
AT robertcunfer homologousandheterologousprotectionofnonhumanprimatesbyebolaandsudanviruslikeparticles
AT frederickwholtsberg homologousandheterologousprotectionofnonhumanprimatesbyebolaandsudanviruslikeparticles
AT sergeyshulenin homologousandheterologousprotectionofnonhumanprimatesbyebolaandsudanviruslikeparticles
AT hongvu homologousandheterologousprotectionofnonhumanprimatesbyebolaandsudanviruslikeparticles
AT danalswenson homologousandheterologousprotectionofnonhumanprimatesbyebolaandsudanviruslikeparticles
AT sinabavari homologousandheterologousprotectionofnonhumanprimatesbyebolaandsudanviruslikeparticles
AT mjavadaman homologousandheterologousprotectionofnonhumanprimatesbyebolaandsudanviruslikeparticles