Bissinger T, Fritsch J, Mihut A, Wu Y, Liu X, Genzel Y, Tan W-S, Reichl U (2019) Semi-perfusion cultures of suspension MDCK cells enable high cell concentrations and efficient influenza A virus production. Vaccine 37(47):7003-7010 doi:10.1016/j.vaccine.2019.04.054
Bock A, Sann H, Schulze-Horsel J, Genzel Y, Reichl U, Mohler L (2009) Growth behavior of number distributed adherent MDCK cells for optimization in microcarrier cultures. Biotechnol Prog 25(6):1717-31 doi:10.1002/btpr.262
Brown SW, Mehtali M (2010) The Avian EB66® Cell Line, Application to Vaccines, and Therapeutic Protein Production. PDA J Pharm Sci Technol 64(5):419
Chu C, Lugovtsev V, Golding H, Betenbaugh M, Shiloach J (2009) Conversion of MDCK cell line to suspension culture by transfecting with human siat7e gene and its application for influenza virus production. PNAS 106(35):14802-14807 doi:www.pnas.org/cgi/doi/10.1073/pnas.0905912106
Coronel J, Behrendt I, Burgin T, Anderlei T, Sandig V, Reichl U, Genzel Y (2019) Influenza A virus production in a single-use orbital shaken bioreactor with ATF or TFF perfusion systems. Vaccine 37(47):7011-7018 doi:10.1016/j.vaccine.2019.06.005
Cruz HJ, Freitas CM, Alves PM, Moreira JL, Carrondo MJT (2000) Effects of ammonia and lactate on growth, metabolism, and productivity of BHK cells. Enzyme and Microbial Technology 27(1):43-52 doi:https://doi.org/10.1016/S0141-0229(00)00151-4
Frensing T, Heldt FS, Pflugmacher A, Behrendt I, Jordan I, Flockerzi D, Genzel Y, Reichl U (2013) Continuous influenza virus production in cell culture shows a periodic accumulation of defective interfering particles. PLoS One 8(9):e72288 doi:10.1371/journal.pone.0072288
Gao M, Cao C, Ma H, Zhu C, Jia Q (2016) Comparative study of two kinds of cell counting methods in cytotoxicity test. Journal of Medical Pest Control 32(12):1313-1316
Genzel Y, Dietzsch C, Rapp E, Schwarzer J, Reichl U (2010) MDCK and Vero cells for influenza virus vaccine production: a one-to-one comparison up to lab-scale bioreactor cultivation. Appl Microbiol Biotechnol 88(2):461-75 doi:10.1007/s00253-010-2742-9
Genzel Y, Olmer RM, Schafer B, Reichl U (2006) Wave microcarrier cultivation of MDCK cells for influenza virus production in serum containing and serum-free media. Vaccine 24(35-36):6074-87 doi:10.1016/j.vaccine.2006.05.023
Genzel Y, Reichl U (2009) Continuous cell lines as a production system for influenza vaccines. Expert Rev Vaccines 8(12):1681-1692
Genzel Y, Vogel T, Buck J, Behrendt I, Ramirez DV, Schiedner G, Jordan I, Reichl U (2014) High cell density cultivations by alternating tangential flow (ATF) perfusion for influenza A virus production using suspension cells. Vaccine 32(24):2770-81 doi:10.1016/j.vaccine.2014.02.016
Granicher G, Coronel J, Pralow A, Marichal-Gallardo P, Wolff M, Rapp E, Karlas A, Sandig V, Genzel Y, Reichl U (2019) Efficient influenza A virus production in high cell density using the novel porcine suspension cell line PBG.PK2.1. Vaccine 37(47):7019-7028 doi:10.1016/j.vaccine.2019.04.030
Gu M, Xu L, Wang X, Liu X (2017) Current situation of H9N2 subtype avian influenza in China. Vet Res 48(1):49 doi:10.1186/s13567-017-0453-2
Harding AT, Heaton NS (2018) Efforts to Improve the Seasonal Influenza Vaccine. Vaccines (Basel) 6(2) doi:10.3390/vaccines6020019
Hegde NR (2015) Cell culture-based influenza vaccines: A necessary and indispensable investment for the future. Hum Vaccin Immunother 11(5):1223-34 doi:10.1080/21645515.2015.1016666
Hu AY, Weng TC, Tseng YF, Chen YS, Wu CH, Hsiao S, Chou AH, Chao HJ, Gu A, Wu SC, Chong P, Lee MS (2008) Microcarrier-based MDCK cell culture system for the production of influenza H5N1 vaccines. Vaccine 26(45):5736-40 doi:10.1016/j.vaccine.2008.08.015
Huang D, Peng WJ, Ye Q, Liu XP, Zhao L, Fan L, Xia-Hou K, Jia HJ, Luo J, Zhou LT, Li BB, Wang SL, Xu WT, Chen Z, Tan WS (2015) Serum-free suspension culture of MDCK cells for production of influenza H1N1 vaccines. PLoS One 10(11):e0141686 doi:10.1371/journal.pone.0141686
Huang D, Xia-Hou K, Liu X-P, Zhao L, Fan L, Ye Z, Tan W-S, Luo J, Chen Z (2014) Rational design of medium supplementation strategy for improved influenza viruses production based on analyzing nutritional requirements of MDCK Cells. Vaccine 32:7091-7097 doi:10.1016/j.vaccine.2014.10.067
Huang D, Zhao L, Tan W (2011) Adherent and single-cell suspension culture of Madin-Darby canine kidney cells in serum-free medium. Chin J Biotechnol/Shengwu Gongcheng Xuebao 27:645-52
Hussain AI, Cordeiro M, Sevilla E, Liu J (2010) Comparison of egg and high yielding MDCK cell-derived live attenuated influenza virus for commercial production of trivalent influenza vaccine: in vitro cell susceptibility and influenza virus replication kinetics in permissive and semi-permissive cells. Vaccine 28(22):3848-55 doi:10.1016/j.vaccine.2010.03.005
Kalbfuss B, Knöchlein A, Kröber T, Reichl U (2008) Monitoring influenza virus content in vaccine production: Precise assays for the quantitation of hemagglutination and neuraminidase activity. Biologicals 36(3):145-161 doi:10.1016/j.biologicals.2007.10.002
Lamb RA, Takeda M (2001) Death by influenza virus protein. Nat Med 7(12):1286-1288 doi:10.1038/nm1201-1286
Lao M-S, Toth D (1997) Effects of Ammonium and Lactate on Growth and Metabolism of a Recombinant Chinese Hamster Ovary Cell Culture. Biotechnology Progress 13(5):688-691 doi:10.1021/bp9602360
Le Ru A, Jacob D, Transfiguracion J, Ansorge S, Henry O, Kamen AA (2010) Scalable production of influenza virus in HEK-293 cells for efficient vaccine manufacturing. Vaccine 28(21):3661-71 doi:10.1016/j.vaccine.2010.03.029
Lee D-H, Song C-S (2013) H9N2 avian influenza virus in Korea: evolution and vaccination. Clin Exp Vaccine Res 2(1):26-33 doi:10.7774/cevr.2013.2.1.26
Li C, Xiao J, Li X, Liu D (2009) Research on multiplication of the H9N2 subtype avian influenza virus in large-scale microcarrier-based MDCK cell culture system. Chin J Zoonoses 25(12):1149-1153
Li L, Du X, Zhang L, Yang L, Gao X, Tang D, Zhao H, Jiang X, Zhang T, Li J (2018) Optimization of Cultivation Conditions for Reassortant Avian Influenza Virus. Scientia Agricultura Sinica 51(17):3415-3426 doi: 10.3864/j.issn.0578-1752.2018.17.016
Li X, Shi J, Guo J, Deng G, Zhang Q, Wang J, He X, Wang K, Chen J, Li Y, Fan J, Kong H, Gu C, Guan Y, Suzuki Y, Kawaoka Y, Liu L, Jiang Y, Tian G, Li Y, Bu Z, Chen H (2014) Genetics, receptor binding property, and transmissibility in mammals of naturally isolated H9N2 Avian Influenza viruses. PLoS Pathog 10(11):e1004508-e1004508 doi:10.1371/journal.ppat.1004508
Lohr V, Genzel Y, Behrendt I, Scharfenberg K, Reichl U (2010) A new MDCK suspension line cultivated in a fully defined medium in stirred-tank and wave bioreactor. Vaccine 28(38):6256-64 doi:10.1016/j.vaccine.2010.07.004
Lohr V, Rath A, Genzel Y, Jordan I, Sandig V, Reichl U (2009) New avian suspension cell lines provide production of influenza virus and MVA in serum-free media: studies on growth, metabolism and virus propagation. Vaccine 27(36):4975-82 doi:10.1016/j.vaccine.2009.05.083
Maranga L, Brazao TF, Carrondo MJ (2003) Virus-like particle production at low multiplicities of infection with the baculovirus insect cell system. Biotechnol Bioeng 84(2):245-53 doi:10.1002/bit.10773
Milian E, Kamen AA (2015) Current and emerging cell culture manufacturing technologies for influenza vaccines. Biomed Res Int:1-11 doi:10.1155/2015/504831
Nikolay A, Bissinger T, Gränicher G, Wu Y, Genzel Y, Reichl U (2020) Perfusion Control for High Cell Density Cultivation and Viral Vaccine Production. In: Pörtner R (ed) Animal Cell Biotechnology: Methods and Protocols. Springer US, New York, NY, pp 141-168
Park K, Kwon H-I, Song M-S, Pascua PN, Baek Y, Lee JH, Jang H-L, Lim J-Y, Mo I-P, Moon H, Kim C-J, Choi YK (2011) Rapid evolution of low-pathogenic H9N2 avian influenza viruses following poultry vaccination programmes. J Gen Virol 92:36-50 doi:10.1099/vir.0.024992-0
Pau MG, Ophorst C, Koldijk MH, Schouten G, Mehtali M, Uytdehaag F (2001) The human cell line PER.C6 provides a new manufacturing system for the production of influenza vaccines. Vaccine 19(17):2716-2721 doi:https://doi.org/10.1016/S0264-410X(00)00508-9
Pedersen JC (2008) Hemagglutination-Inhibition Test for Avian Influenza Virus Subtype Identification and the Detection and Quantitation of Serum Antibodies to the Avian Influenza Virus. In: Spackman E (ed) Avian Influenza Virus. Humana Press, Totowa, NJ, pp 53-66
Peschel B, Frentzel S, Laske T, Genzel Y, Reichl U (2013) Comparison of influenza virus yields and apoptosis-induction in an adherent and a suspension MDCK cell line. Vaccine 31(48):5693-9 doi:10.1016/j.vaccine.2013.09.051
Petiot E, Proust A, Traversier A, Durous L, Dappozze F, Gras M, Guillard C, Balloul JM, Rosa-Calatrava M (2018) Influenza viruses production: Evaluation of a novel avian cell line DuckCelt(R)-T17. Vaccine 36(22):3101-3111 doi:10.1016/j.vaccine.2017.03.102
Pu J, Sun H, Qu Y, Wang C, Gao W, Zhu J, Sun Y, Bi Y, Huang Y, Chang K-C, Cui J, Liu J (2017) M Gene Reassortment in H9N2 Influenza Virus Promotes Early Infection and Replication: Contribution to Rising Virus Prevalence in Chickens in China. J Virol 91:JVI.02055-16 doi:10.1128/JVI.02055-16
Pu J, Wang S, Yin Y, Zhang G, Carter R, Wang J, Xu G, Sun H, Wang M, Wen C, Wei Y, Wang D, Zhu B, Lemmon G, Jiao Y, Duan S, Wang Q, Du Q, Sun M, Webster R (2015) Evolution of the H9N2 influenza genotype that facilitated the genesis of the novel H7N9 virus. Proc Natl Acad Sci USA 112:548-553 doi:10.1073/pnas.1422456112
Ren Z, Lu Z, Wang L, Huo Z, Cui J, Zheng T, Dai Q, Chen C, Qin M, Chen M, Yang R (2015) Rapid production of a H9N2 influenza vaccine from MDCK cells for protecting chicken against influenza virus infection. Appl Microbiol Biotechnol 99(7):2999-3013 doi:10.1007/s00253-015-6406-7
Ritter JB, Wahl AS, Freund S, Genzel Y, Reichl U (2010) Metabolic effects of influenza virus infection in cultured animal cells: Intra- and extracellular metabolite profiling. BMC systems biology 4(61):1-22 doi:10.1186/1752-0509-4-61
Sorrell E, Wan H, Araya Y, Song H, Perez D (2009) Minimal molecular constraints for respiratory droplet transmission of an avian-human H9N2 influenza A virus. Proc Natl Acad Sci USA 106:7565-70 doi:10.1073/pnas.0900877106
Sun K, Ye J, Perez DR, Metzger DW (2011) Seasonal FluMist vaccination induces cross-reactive T cell immunity against H1N1 (2009) influenza and secondary bacterial infections. J Immunol 186(2):987-993 doi:10.4049/jimmunol.1002664
Tapia F, Vazquez-Ramirez D, Genzel Y, Reichl U (2016) Bioreactors for high cell density and continuous multi-stage cultivations: options for process intensification in cell culture-based viral vaccine production. Appl Microbiol Biotechnol 100(5):2121-32 doi:10.1007/s00253-015-7267-9
Ulmer JB, Valley U, Rappuoli R (2006) Vaccine manufacturing: challenges and solutions. Nat Biotechnol 24(11):1377-1383 doi:10.1038/nbt1261
van Wielink R, Kant-Eenbergen HC, Harmsen MM, Martens DE, Wijffels RH, Coco-Martin JM (2011) Adaptation of a Madin-Darby canine kidney cell line to suspension growth in serum-free media and comparison of its ability to produce avian influenza virus to Vero and BHK21 cell lines. J Virol Methods 171(1):53-60 doi:10.1016/j.jviromet.2010.09.029
Wang H, Guo S, Li Z, Xu X, Shao Z, Song G (2017) Suspension culture process for H9N2 avian influenza virus (strain Re-2). Arch Virol 162(10):3051-3059 doi:10.1007/s00705-017-3460-8
Zost SJ, Parkhouse K, Gumina ME, Kim K, Diaz Perez S, Wilson PC, Treanor JJ, Sant AJ, Cobey S, Hensley SE (2017) Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains. Proc Natl Acad Sci U S A 114(47):12578-12583 doi:10.1073/pnas.1712377114