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Effects of adjuvants in a rabies-vectored Ebola virus vaccine on protection from surrogate challenge

Ebola virus is the primary contributor to the global threat of filovirus severe hemorrhagic fever, and Ebola virus disease has a case fatality rate of 50–90%. An inactivated, bivalent filovirus/rabies virus vaccine, FILORAB1, consists of recombinant rabies virus virions expressing the Ebola virus gl...

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Autores principales: Yankowski, Catherine, Kurup, Drishya, Wirblich, Christoph, Schnell, Matthias J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9906604/
https://www.ncbi.nlm.nih.gov/pubmed/36754965
http://dx.doi.org/10.1038/s41541-023-00615-z
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author Yankowski, Catherine
Kurup, Drishya
Wirblich, Christoph
Schnell, Matthias J.
author_facet Yankowski, Catherine
Kurup, Drishya
Wirblich, Christoph
Schnell, Matthias J.
author_sort Yankowski, Catherine
collection PubMed
description Ebola virus is the primary contributor to the global threat of filovirus severe hemorrhagic fever, and Ebola virus disease has a case fatality rate of 50–90%. An inactivated, bivalent filovirus/rabies virus vaccine, FILORAB1, consists of recombinant rabies virus virions expressing the Ebola virus glycoprotein. FILORAB1 is immunogenic and protective from Ebola virus challenge in mice and non-human primates, and protection is enhanced when formulated with toll-like receptor 4 agonist Glucopyranosyl lipid adjuvant (GLA) in a squalene oil-in-water emulsion (SE). Through an adjuvant comparison in mice, we demonstrate that GLA-SE improves FILORAB1 efficacy by activating the innate immune system and shaping a Th1-biased adaptive immune response. GLA-SE adjuvanted mice and those adjuvanted with the SE component are better protected from surrogate challenge, while Th2 alum adjuvanted mice are not. Additionally, the immune response to FILORAB1 is long-lasting, as exhibited by highly-maintained serum antibody titers and long-lived cells in the spleen and bone marrow.
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spelling pubmed-99066042023-02-08 Effects of adjuvants in a rabies-vectored Ebola virus vaccine on protection from surrogate challenge Yankowski, Catherine Kurup, Drishya Wirblich, Christoph Schnell, Matthias J. NPJ Vaccines Article Ebola virus is the primary contributor to the global threat of filovirus severe hemorrhagic fever, and Ebola virus disease has a case fatality rate of 50–90%. An inactivated, bivalent filovirus/rabies virus vaccine, FILORAB1, consists of recombinant rabies virus virions expressing the Ebola virus glycoprotein. FILORAB1 is immunogenic and protective from Ebola virus challenge in mice and non-human primates, and protection is enhanced when formulated with toll-like receptor 4 agonist Glucopyranosyl lipid adjuvant (GLA) in a squalene oil-in-water emulsion (SE). Through an adjuvant comparison in mice, we demonstrate that GLA-SE improves FILORAB1 efficacy by activating the innate immune system and shaping a Th1-biased adaptive immune response. GLA-SE adjuvanted mice and those adjuvanted with the SE component are better protected from surrogate challenge, while Th2 alum adjuvanted mice are not. Additionally, the immune response to FILORAB1 is long-lasting, as exhibited by highly-maintained serum antibody titers and long-lived cells in the spleen and bone marrow. Nature Publishing Group UK 2023-02-08 /pmc/articles/PMC9906604/ /pubmed/36754965 http://dx.doi.org/10.1038/s41541-023-00615-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Yankowski, Catherine
Kurup, Drishya
Wirblich, Christoph
Schnell, Matthias J.
Effects of adjuvants in a rabies-vectored Ebola virus vaccine on protection from surrogate challenge
title Effects of adjuvants in a rabies-vectored Ebola virus vaccine on protection from surrogate challenge
title_full Effects of adjuvants in a rabies-vectored Ebola virus vaccine on protection from surrogate challenge
title_fullStr Effects of adjuvants in a rabies-vectored Ebola virus vaccine on protection from surrogate challenge
title_full_unstemmed Effects of adjuvants in a rabies-vectored Ebola virus vaccine on protection from surrogate challenge
title_short Effects of adjuvants in a rabies-vectored Ebola virus vaccine on protection from surrogate challenge
title_sort effects of adjuvants in a rabies-vectored ebola virus vaccine on protection from surrogate challenge
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9906604/
https://www.ncbi.nlm.nih.gov/pubmed/36754965
http://dx.doi.org/10.1038/s41541-023-00615-z
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