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Elements in the Development of a Production Process for Modified Vaccinia Virus Ankara

The production of several viral vaccines depends on chicken embryo fibroblasts or embryonated chicken eggs. To replace this logistically demanding substrate, we created continuous anatine suspension cell lines (CR and CR.pIX), developed chemically-defined media, and established production processes...

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Autores principales: Jordan, Ingo, Lohr, Verena, Genzel, Yvonne, Reichl, Udo, Sandig, Volker
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029493/
https://www.ncbi.nlm.nih.gov/pubmed/27694766
http://dx.doi.org/10.3390/microorganisms1010100
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author Jordan, Ingo
Lohr, Verena
Genzel, Yvonne
Reichl, Udo
Sandig, Volker
author_facet Jordan, Ingo
Lohr, Verena
Genzel, Yvonne
Reichl, Udo
Sandig, Volker
author_sort Jordan, Ingo
collection PubMed
description The production of several viral vaccines depends on chicken embryo fibroblasts or embryonated chicken eggs. To replace this logistically demanding substrate, we created continuous anatine suspension cell lines (CR and CR.pIX), developed chemically-defined media, and established production processes for different vaccine viruses. One of the processes investigated in greater detail was developed for modified vaccinia virus Ankara (MVA). MVA is highly attenuated for human recipients and an efficient vector for reactogenic expression of foreign genes. Because direct cell-to-cell spread is one important mechanism for vaccinia virus replication, cultivation of MVA in bioreactors is facilitated if cell aggregates are induced after infection. This dependency may be the mechanism behind our observation that a novel viral genotype (MVA-CR) accumulates with serial passage in suspension cultures. Sequencing of a major part of the genomic DNA of the new strain revealed point mutations in three genes. We hypothesize that these changes confer an advantage because they may allow a greater fraction of MVA-CR viruses to escape the host cells for infection of distant targets. Production and purification of MVA-based vaccines may be simplified by this combination of designed avian cell line, chemically defined media and the novel virus strain.
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spelling pubmed-50294932016-09-28 Elements in the Development of a Production Process for Modified Vaccinia Virus Ankara Jordan, Ingo Lohr, Verena Genzel, Yvonne Reichl, Udo Sandig, Volker Microorganisms Review The production of several viral vaccines depends on chicken embryo fibroblasts or embryonated chicken eggs. To replace this logistically demanding substrate, we created continuous anatine suspension cell lines (CR and CR.pIX), developed chemically-defined media, and established production processes for different vaccine viruses. One of the processes investigated in greater detail was developed for modified vaccinia virus Ankara (MVA). MVA is highly attenuated for human recipients and an efficient vector for reactogenic expression of foreign genes. Because direct cell-to-cell spread is one important mechanism for vaccinia virus replication, cultivation of MVA in bioreactors is facilitated if cell aggregates are induced after infection. This dependency may be the mechanism behind our observation that a novel viral genotype (MVA-CR) accumulates with serial passage in suspension cultures. Sequencing of a major part of the genomic DNA of the new strain revealed point mutations in three genes. We hypothesize that these changes confer an advantage because they may allow a greater fraction of MVA-CR viruses to escape the host cells for infection of distant targets. Production and purification of MVA-based vaccines may be simplified by this combination of designed avian cell line, chemically defined media and the novel virus strain. MDPI 2013-11-01 /pmc/articles/PMC5029493/ /pubmed/27694766 http://dx.doi.org/10.3390/microorganisms1010100 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Review
Jordan, Ingo
Lohr, Verena
Genzel, Yvonne
Reichl, Udo
Sandig, Volker
Elements in the Development of a Production Process for Modified Vaccinia Virus Ankara
title Elements in the Development of a Production Process for Modified Vaccinia Virus Ankara
title_full Elements in the Development of a Production Process for Modified Vaccinia Virus Ankara
title_fullStr Elements in the Development of a Production Process for Modified Vaccinia Virus Ankara
title_full_unstemmed Elements in the Development of a Production Process for Modified Vaccinia Virus Ankara
title_short Elements in the Development of a Production Process for Modified Vaccinia Virus Ankara
title_sort elements in the development of a production process for modified vaccinia virus ankara
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029493/
https://www.ncbi.nlm.nih.gov/pubmed/27694766
http://dx.doi.org/10.3390/microorganisms1010100
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