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Replication-Deficient Particles: New Insights into the Next Generation of Bluetongue Virus Vaccines
Bluetongue virus (BTV) is endemic in many parts of the world, often causing severe hemorrhagic disease in livestock. To date, at least 27 different serotypes have been recognized. Vaccination against all serotypes is necessary to protect susceptible animals and to prevent onward spread of the virus...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5165199/ https://www.ncbi.nlm.nih.gov/pubmed/27795442 http://dx.doi.org/10.1128/JVI.01892-16 |
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author | Celma, Cristina C. Stewart, Meredith Wernike, Kerstin Eschbaumer, Michael Gonzalez-Molleda, Lorenzo Breard, Emmanuel Schulz, Claudia Hoffmann, Bernd Haegeman, Andy De Clercq, Kris Zientara, Stephan van Rijn, Piet A. Beer, Martin Roy, Polly |
author_facet | Celma, Cristina C. Stewart, Meredith Wernike, Kerstin Eschbaumer, Michael Gonzalez-Molleda, Lorenzo Breard, Emmanuel Schulz, Claudia Hoffmann, Bernd Haegeman, Andy De Clercq, Kris Zientara, Stephan van Rijn, Piet A. Beer, Martin Roy, Polly |
author_sort | Celma, Cristina C. |
collection | PubMed |
description | Bluetongue virus (BTV) is endemic in many parts of the world, often causing severe hemorrhagic disease in livestock. To date, at least 27 different serotypes have been recognized. Vaccination against all serotypes is necessary to protect susceptible animals and to prevent onward spread of the virus by insect vectors. In our previous studies, we generated replication-deficient (disabled infectious single-cycle [DISC]) virus strains for a number of serotypes and reported preliminary data on their protective efficacy in animals. In this report, to advance the DISC vaccines to the marketplace, we investigated different parameters of these DISC vaccines. First, we demonstrated the genetic stabilities of these vaccine strains and also the complementing cell line. Subsequently, the optimal storage conditions of vaccines, including additives, temperature, and desiccation, were determined and their protective efficacies in animals confirmed. Furthermore, to test if mixtures of different vaccine strains could be tolerated, we tested cocktails of DISC vaccines in combinations of three or six different serotypes in sheep and cattle, the two natural hosts of BTV. Groups of sheep vaccinated with a cocktail of six different vaccines were completely protected from challenge with individual virulent serotypes, both in early challenge and after 5 months of challenge without any clinical disease. There was no interference in protection between the different vaccines. Protection was also achieved in cattle with a mixture of three vaccine strains, albeit at a lesser level than in sheep. Our data support and validate the suitability of these virus strains as the next-generation vaccines for BTV. IMPORTANCE Bluetongue (BT) is a debilitating and in many cases lethal disease that affects ruminants of economic importance. Classical vaccines that afford protection against bluetongue virus, the etiological agent, are not free from secondary and undesirable effects. A surge in new approaches to produce highly attenuated, safer vaccines was evident after the development of the BTV reverse-genetics system that allows the introduction of targeted mutations in the virus genome. We targeted an essential gene to develop disabled virus strains as vaccine candidates. The results presented in this report further substantiate our previous evidence and support the suitability of these virus strains as the next-generation BTV vaccines. |
format | Online Article Text |
id | pubmed-5165199 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-51651992017-01-09 Replication-Deficient Particles: New Insights into the Next Generation of Bluetongue Virus Vaccines Celma, Cristina C. Stewart, Meredith Wernike, Kerstin Eschbaumer, Michael Gonzalez-Molleda, Lorenzo Breard, Emmanuel Schulz, Claudia Hoffmann, Bernd Haegeman, Andy De Clercq, Kris Zientara, Stephan van Rijn, Piet A. Beer, Martin Roy, Polly J Virol Pathogenesis and Immunity Bluetongue virus (BTV) is endemic in many parts of the world, often causing severe hemorrhagic disease in livestock. To date, at least 27 different serotypes have been recognized. Vaccination against all serotypes is necessary to protect susceptible animals and to prevent onward spread of the virus by insect vectors. In our previous studies, we generated replication-deficient (disabled infectious single-cycle [DISC]) virus strains for a number of serotypes and reported preliminary data on their protective efficacy in animals. In this report, to advance the DISC vaccines to the marketplace, we investigated different parameters of these DISC vaccines. First, we demonstrated the genetic stabilities of these vaccine strains and also the complementing cell line. Subsequently, the optimal storage conditions of vaccines, including additives, temperature, and desiccation, were determined and their protective efficacies in animals confirmed. Furthermore, to test if mixtures of different vaccine strains could be tolerated, we tested cocktails of DISC vaccines in combinations of three or six different serotypes in sheep and cattle, the two natural hosts of BTV. Groups of sheep vaccinated with a cocktail of six different vaccines were completely protected from challenge with individual virulent serotypes, both in early challenge and after 5 months of challenge without any clinical disease. There was no interference in protection between the different vaccines. Protection was also achieved in cattle with a mixture of three vaccine strains, albeit at a lesser level than in sheep. Our data support and validate the suitability of these virus strains as the next-generation vaccines for BTV. IMPORTANCE Bluetongue (BT) is a debilitating and in many cases lethal disease that affects ruminants of economic importance. Classical vaccines that afford protection against bluetongue virus, the etiological agent, are not free from secondary and undesirable effects. A surge in new approaches to produce highly attenuated, safer vaccines was evident after the development of the BTV reverse-genetics system that allows the introduction of targeted mutations in the virus genome. We targeted an essential gene to develop disabled virus strains as vaccine candidates. The results presented in this report further substantiate our previous evidence and support the suitability of these virus strains as the next-generation BTV vaccines. American Society for Microbiology 2016-12-16 /pmc/articles/PMC5165199/ /pubmed/27795442 http://dx.doi.org/10.1128/JVI.01892-16 Text en Copyright © 2016 Celma et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Pathogenesis and Immunity Celma, Cristina C. Stewart, Meredith Wernike, Kerstin Eschbaumer, Michael Gonzalez-Molleda, Lorenzo Breard, Emmanuel Schulz, Claudia Hoffmann, Bernd Haegeman, Andy De Clercq, Kris Zientara, Stephan van Rijn, Piet A. Beer, Martin Roy, Polly Replication-Deficient Particles: New Insights into the Next Generation of Bluetongue Virus Vaccines |
title | Replication-Deficient Particles: New Insights into the Next Generation of Bluetongue Virus Vaccines |
title_full | Replication-Deficient Particles: New Insights into the Next Generation of Bluetongue Virus Vaccines |
title_fullStr | Replication-Deficient Particles: New Insights into the Next Generation of Bluetongue Virus Vaccines |
title_full_unstemmed | Replication-Deficient Particles: New Insights into the Next Generation of Bluetongue Virus Vaccines |
title_short | Replication-Deficient Particles: New Insights into the Next Generation of Bluetongue Virus Vaccines |
title_sort | replication-deficient particles: new insights into the next generation of bluetongue virus vaccines |
topic | Pathogenesis and Immunity |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5165199/ https://www.ncbi.nlm.nih.gov/pubmed/27795442 http://dx.doi.org/10.1128/JVI.01892-16 |
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