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A Rift Valley fever virus Gn ectodomain-based DNA vaccine induces a partial protection not improved by APC targeting

Rift Valley fever virus, a phlebovirus endemic in Africa, causes serious diseases in ruminants and humans. Due to the high probability of new outbreaks and spread to other continents where competent vectors are present, vaccine development is an urgent priority as no licensed vaccines are available...

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Autores principales: Chrun, Tiphany, Lacôte, Sandra, Urien, Céline, Jouneau, Luc, Barc, Céline, Bouguyon, Edwige, Contreras, Vanessa, Ferrier-Rembert, Audrey, Peyrefitte, Christophe N., Busquets, Nuria, Vidal, Enric, Pujols, Joan, Marianneau, Philippe, Schwartz-Cornil, Isabelle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5910381/
https://www.ncbi.nlm.nih.gov/pubmed/29707242
http://dx.doi.org/10.1038/s41541-018-0052-x
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author Chrun, Tiphany
Lacôte, Sandra
Urien, Céline
Jouneau, Luc
Barc, Céline
Bouguyon, Edwige
Contreras, Vanessa
Ferrier-Rembert, Audrey
Peyrefitte, Christophe N.
Busquets, Nuria
Vidal, Enric
Pujols, Joan
Marianneau, Philippe
Schwartz-Cornil, Isabelle
author_facet Chrun, Tiphany
Lacôte, Sandra
Urien, Céline
Jouneau, Luc
Barc, Céline
Bouguyon, Edwige
Contreras, Vanessa
Ferrier-Rembert, Audrey
Peyrefitte, Christophe N.
Busquets, Nuria
Vidal, Enric
Pujols, Joan
Marianneau, Philippe
Schwartz-Cornil, Isabelle
author_sort Chrun, Tiphany
collection PubMed
description Rift Valley fever virus, a phlebovirus endemic in Africa, causes serious diseases in ruminants and humans. Due to the high probability of new outbreaks and spread to other continents where competent vectors are present, vaccine development is an urgent priority as no licensed vaccines are available outside areas of endemicity. In this study, we evaluated in sheep the protective immunity induced by DNA vaccines encoding the extracellular portion of the Gn antigen which was either or not targeted to antigen-presenting cells. The DNA encoding untargeted antigen was the most potent at inducing IgG responses, although not neutralizing, and conferred a significant clinical and virological protection upon infectious challenge, superior to DNA vaccines encoding the targeted antigen. A statistical analysis of the challenge parameters supported that the anti-eGn IgG, rather than the T-cell response, was instrumental in protection. Altogether, this work shows that a DNA vaccine encoding the extracellular portion of the Gn antigen confers substantial—although incomplete—protective immunity in sheep, a natural host with high preclinical relevance, and provides some insights into key immune correlates useful for further vaccine improvements against the Rift Valley fever virus.
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spelling pubmed-59103812018-04-27 A Rift Valley fever virus Gn ectodomain-based DNA vaccine induces a partial protection not improved by APC targeting Chrun, Tiphany Lacôte, Sandra Urien, Céline Jouneau, Luc Barc, Céline Bouguyon, Edwige Contreras, Vanessa Ferrier-Rembert, Audrey Peyrefitte, Christophe N. Busquets, Nuria Vidal, Enric Pujols, Joan Marianneau, Philippe Schwartz-Cornil, Isabelle NPJ Vaccines Article Rift Valley fever virus, a phlebovirus endemic in Africa, causes serious diseases in ruminants and humans. Due to the high probability of new outbreaks and spread to other continents where competent vectors are present, vaccine development is an urgent priority as no licensed vaccines are available outside areas of endemicity. In this study, we evaluated in sheep the protective immunity induced by DNA vaccines encoding the extracellular portion of the Gn antigen which was either or not targeted to antigen-presenting cells. The DNA encoding untargeted antigen was the most potent at inducing IgG responses, although not neutralizing, and conferred a significant clinical and virological protection upon infectious challenge, superior to DNA vaccines encoding the targeted antigen. A statistical analysis of the challenge parameters supported that the anti-eGn IgG, rather than the T-cell response, was instrumental in protection. Altogether, this work shows that a DNA vaccine encoding the extracellular portion of the Gn antigen confers substantial—although incomplete—protective immunity in sheep, a natural host with high preclinical relevance, and provides some insights into key immune correlates useful for further vaccine improvements against the Rift Valley fever virus. Nature Publishing Group UK 2018-04-20 /pmc/articles/PMC5910381/ /pubmed/29707242 http://dx.doi.org/10.1038/s41541-018-0052-x Text en © The Author(s) 2018 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/.
spellingShingle Article
Chrun, Tiphany
Lacôte, Sandra
Urien, Céline
Jouneau, Luc
Barc, Céline
Bouguyon, Edwige
Contreras, Vanessa
Ferrier-Rembert, Audrey
Peyrefitte, Christophe N.
Busquets, Nuria
Vidal, Enric
Pujols, Joan
Marianneau, Philippe
Schwartz-Cornil, Isabelle
A Rift Valley fever virus Gn ectodomain-based DNA vaccine induces a partial protection not improved by APC targeting
title A Rift Valley fever virus Gn ectodomain-based DNA vaccine induces a partial protection not improved by APC targeting
title_full A Rift Valley fever virus Gn ectodomain-based DNA vaccine induces a partial protection not improved by APC targeting
title_fullStr A Rift Valley fever virus Gn ectodomain-based DNA vaccine induces a partial protection not improved by APC targeting
title_full_unstemmed A Rift Valley fever virus Gn ectodomain-based DNA vaccine induces a partial protection not improved by APC targeting
title_short A Rift Valley fever virus Gn ectodomain-based DNA vaccine induces a partial protection not improved by APC targeting
title_sort rift valley fever virus gn ectodomain-based dna vaccine induces a partial protection not improved by apc targeting
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5910381/
https://www.ncbi.nlm.nih.gov/pubmed/29707242
http://dx.doi.org/10.1038/s41541-018-0052-x
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