scholarly journals Madin‐Darby canine kidney cell sialic acid receptor modulation induced by culture medium conditions: Implications for the isolation of influenza A virus

2019 ◽  
Vol 13 (6) ◽  
pp. 593-602 ◽  
Author(s):  
Sarah W. Nelson ◽  
Joshua N. Lorbach ◽  
Jacqueline M. Nolting ◽  
Jason W. Stull ◽  
Daral J. Jackwood ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Influenza A Virus ◽  
Kidney Cell ◽  
Influenza A ◽  
Culture Medium ◽  
Madin Darby Canine Kidney ◽  
Receptor Modulation ◽  
Darby Canine Kidney ◽  
Canine Kidney ◽  
Sialic Acid Receptor

scholarly journals The Madin-Darby canine kidney cell culture derived influenza A/H5N1 vaccine: A Phase I trial in Taiwan

2013 ◽  
Vol 46 (6) ◽  
pp. 448-455 ◽  
Author(s):  
Sung-Ching Pan ◽  
Hsiang-Chi Kung ◽  
Tsui-Mai Kao ◽  
Hsio Wu ◽  
Shao-Xing Dong ◽  
...  
Keyword(s):  
Cell Culture ◽  
Phase I ◽  
Kidney Cell ◽  
Influenza A ◽  
Phase I Trial ◽  
Madin Darby Canine Kidney ◽  
Kidney Cell Culture ◽  
H5n1 Vaccine ◽  
Darby Canine Kidney ◽  
Canine Kidney

scholarly journals A Y161F Hemagglutinin Substitution Increases Thermostability and Improves Yields of 2009 H1N1 Influenza A Virus in Cells

2017 ◽  
Vol 92 (2) ◽  
Author(s):  
Feng Wen ◽  
Lei Li ◽  
Nan Zhao ◽  
Meng-Jung Chiang ◽  
Hang Xie ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Cell Lines ◽  
Mammalian Cell ◽  
Influenza A ◽  
Vero Cells ◽  
Influenza Viruses ◽  
High Yield ◽  
Madin Darby Canine Kidney ◽  
Darby Canine Kidney ◽  
Canine Kidney

ABSTRACTVaccination is the primary strategy for influenza prevention and control. However, egg-based vaccines, the predominant production platform, have several disadvantages, including the emergence of viral antigenic variants that can be induced during egg passage. These limitations have prompted the development of cell-based vaccines, which themselves are not without issue. Most importantly, vaccine seed viruses often do not grow efficiently in mammalian cell lines. Here we aimed to identify novel high-yield signatures for influenza viruses in continuous Madin-Darby canine kidney (MDCK) and Vero cells. Using influenza A(H1N1)pdm09 virus as the testing platform and an integrating error-prone PCR-based mutagenesis strategy, we identified a Y161F mutation in hemagglutinin (HA) that not only enhanced the infectivity of the resultant virus by more than 300-fold but also increased its thermostability without changing its original antigenic properties. The vaccine produced from the Y161F mutant fully protected mice against lethal challenge with wild-type A(H1N1)pdm09. Compared with A(H1N1)pdm09, the Y161F mutant had significantly higher avidity for avian-like and human-like receptor analogs. Of note, the introduction of the Y161F mutation into HA of seasonal H3N2 influenza A virus (IAV) and canine H3N8 IAV also increased yields and thermostability in MDCK cells and chicken embryotic eggs. Thus, residue F161 plays an important role in determining viral growth and thermostability, which could be harnessed to optimize IAV vaccine seed viruses.IMPORTANCEAlthough a promising complement to current egg-based influenza vaccines, cell-based vaccines have one large challenge: high-yield vaccine seeds for production. In this study, we identified a molecular signature, Y161F, in hemagglutinin (HA) that resulted in increased virus growth in Madin-Darby canine kidney and Vero cells, two cell lines commonly used for influenza vaccine manufacturing. This Y161F mutation not only increased HA thermostability but also enhanced its binding affinity for α2,6- and α2,3-linked Neu5Ac. These results suggest that a vaccine strain bearing the Y161F mutation in HA could potentially increase vaccine yields in mammalian cell culture systems.

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