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  Analysis of innate immunity signaling pathways in MDCK cells in an influenza virus vaccine production process

Heynisch, B., Frensing, T., Seitz, C., Genzel, Y., & Reichl, U. (2011). Analysis of innate immunity signaling pathways in MDCK cells in an influenza virus vaccine production process. Poster presented at 22nd ESACT Meeting, Vienna, Austria.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0013-8C25-6 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0025-1AFB-5
Genre: Poster

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 Creators:
Heynisch, Björn1, Author              
Frensing, Timo1, Author              
Seitz, Claudius1, Author              
Genzel, Yvonne1, Author              
Reichl, Udo1, 2, Author              
Affiliations:
1Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, Max Planck Society, ou_1738140              
2Otto-von-Guericke-Universität Magdeburg, ou_1738156              

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 Abstract: Despite tremendous progress in basic research concerning virus-host cell interaction over the past decade, only little efforts have been undertaken to characterize cell culture-based influenza vaccine production. Since manufacturers have to operate within limited time frames to provide sufficient amounts of vaccine, fast, reliable and robust production processes are of crucial importance. This requires a detailed knowledge of cellular events relevant for influenza A virus replication. For instance, it has for a long time remained unclear what role the activation of host cellular innate immunity plays in influenza vaccine production and what impact signaling has on virus yields. In this work, the activation of a number of signaling cascades crucial for influenza A virus replication (NF-κB, IRF-3, PI3K-Akt, Jak-Stat, Raf/MEK/ERK, PKR/eIF2α) was monitored using phospho-specific antibodies. For two variants of influenza virus A/PuertoRico/8/34 H1N1 that replicate to different final titers it could be shown that these pathways are induced stronger by the variant that replicates less well. These results obtained in high multiplicity of infection experiments could be confirmed under bioprocess conditions and in part also at a varying multiplicity of infection. Current efforts are aimed at clarifying the actual significance of the monitored pathways for virus replication by RNAi technology and by the use of small molecule inhibitors. In the long run, these efforts facilitate the understanding of virus replication in cell culture-based vaccine production and might contribute to the design and optimization of production cell lines. [1, 2] [1] Heynisch B, Frensing T, Heinze K, Seitz C, Genzel Y, Reichl U. Differential activation of host cell signalling pathways through infection with two variants of influenza A/Puerto Rico/8/34 (H1N1) in MDCK cells. Vaccine 2010 Nov 29;28(51):8210-8. [2] Seitz C, Frensing T, Hoper D, Kochs G, Reichl U. High yields of influenza A virus in Madin-Darby canine kidney cells are promoted by an insufficient interferon-induced antiviral state. J Gen Virol Jul;91(Pt 7):1754-63.

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Language(s): eng - English
 Dates: 2011
 Publication Status: Not specified
 Pages: -
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 Rev. Method: -
 Identifiers: eDoc: 573853
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Title: 22nd ESACT Meeting
Place of Event: Vienna, Austria
Start-/End Date: 2011-05-15 - 2011-05-18

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