1. Evaluation of a qualified MDCK cell line for virus isolation to develop cell-based influenza vaccine viruses with appropriate antigenicity.
- Author
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Harada Y, Takahashi H, Fujimoto T, Horikoshi F, Chida S, Tanaka K, Minari K, Tanimoto Y, Fujisaki S, Miura H, Nakauchi M, Shimasaki N, Suzuki Y, Arita T, Hamamoto I, Yamamoto N, Hasegawa H, Odagiri T, Tashiro M, and Nobusawa E
- Subjects
- Animals, Dogs, Madin Darby Canine Kidney Cells, Humans, Chlorocebus aethiops, Antibodies, Viral immunology, Neutralization Tests, Vero Cells, Virus Cultivation methods, Influenza A Virus, H3N2 Subtype immunology, Influenza A Virus, H3N2 Subtype genetics, Influenza, Human prevention & control, Influenza, Human immunology, Influenza, Human virology, Influenza A Virus, H1N1 Subtype immunology, Influenza A Virus, H1N1 Subtype genetics, Cell Line, Influenza B virus immunology, Influenza B virus genetics, Influenza Vaccines immunology, Ferrets, Hemagglutination Inhibition Tests methods, Antigens, Viral immunology
- Abstract
We established a qualified Madin-Darby canine kidney cell line (qMDCK-Cs) and investigated its suitability for source virus isolation to develop cell-based seasonal influenza vaccine viruses using vaccine manufacturer cells (Manuf-Cs). When inoculated with 81 influenza-positive clinical specimens, the initial virus isolation efficiency of qMDCK-Cs was exceeded 70%. Among the qMDCK-C isolates, 100% of the A/H1N1pdm09, B/Victoria and B/Yamagata strains and >70% of the A/H3N2 strains showed antigenicity equivalent to that of the contemporary vaccine or relevant viruses in haemagglutination inhibition (HI) or virus neutralization (VN) tests using ferret antisera. These qMDCK-C isolates were propagated in Manuf-Cs (MDCK and Vero cells) (Manuf-C viruses) to develop vaccine viruses. In reciprocal antigenicity tests, ferret antisera raised against corresponding reference viruses and Manuf-C viruses recognized 29 of 31 Manuf-C viruses and corresponding reference viruses, respectively at HI or VN titres more than half of the homologous virus titres, which is the antigenicity criterion for cell culture seasonal influenza vaccine viruses specified by the World Health Organization. Furthermore, ferret antisera against these Manuf-C viruses recognized ≥95% of the viruses circulating during the relevant influenza season with HI or VN titres greater than one-quarter of the homologous virus titres. No cell line-specific amino acid substitutions were observed in the resulting viruses. However, polymorphisms at positions 158/160 of H3HA, 148/151 of N2NA and 197/199 of B/Victoria HA were occasionally detected in the qMDCK-C and Manuf-C viruses but barely affected the viral antigenicity. These results indicated that qMDCK-Cs are suitable for isolating influenza viruses that can serve as a source of antigenically appropriate vaccine viruses. The use of the qMDCK-C isolates will eliminates the need for clinical sample collection, virus isolation, and antigenicity analysis every season, and is expected to contribute to the promotion of vaccine virus development using manufacturer cells., Competing Interests: Declaration of competing interest Takao Fujimoto, Fumiaki Horikoshi, and Shuhei Chida were employees of BIKEN Co., Ltd., Kenji Tanaka is an employee of Daiichi Sankyo Biotech Co., Ltd., Kenji Minari, and Yoshimi Tanimoto are employees of Takeda Pharmaceutical Company Limited., The other coauthors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)
- Published
- 2024
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