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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Main Authors: Volker Sandig, Udo Reichl, Verena Lohr, Yvonne Genzel, Ingo Jordan
Format: Article
Language:English
Published: MDPI AG 2013-11-01
Series:Microorganisms
Subjects:
Online Access:http://www.mdpi.com/2076-2607/1/1/100
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author Volker Sandig
Udo Reichl
Verena Lohr
Yvonne Genzel
Ingo Jordan
author_facet Volker Sandig
Udo Reichl
Verena Lohr
Yvonne Genzel
Ingo Jordan
author_sort Volker Sandig
collection DOAJ
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 doaj.art-825292b1b41540fa85509e2b13dfbcb72022-12-22T01:56:03ZengMDPI AGMicroorganisms2076-26072013-11-011110012110.3390/microorganisms1010100Elements in the Development of a Production Process for Modified Vaccinia Virus AnkaraVolker SandigUdo ReichlVerena LohrYvonne GenzelIngo JordanThe 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.http://www.mdpi.com/2076-2607/1/1/100AGE1.CR.pImuscovy duck continuous cell linemodified vaccinia virus AnkaraMVA (modified vaccinia virus Ankara)
spellingShingle Volker Sandig
Udo Reichl
Verena Lohr
Yvonne Genzel
Ingo Jordan
Elements in the Development of a Production Process for Modified Vaccinia Virus Ankara
Microorganisms
AGE1.CR.pI
muscovy duck continuous cell line
modified vaccinia virus Ankara
MVA (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 AGE1.CR.pI
muscovy duck continuous cell line
modified vaccinia virus Ankara
MVA (modified vaccinia virus Ankara)
url http://www.mdpi.com/2076-2607/1/1/100
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