Trypsin promotes efficient influenza vaccine production in MDCK cells by interfering with the antiviral host response

Applied Microbiology and Biotechnology

Volumn 93, Issue 2, 2012, Pages 601-611

  Seitz, Claudius ^a   Isken, Britta ^a   Heynisch, Björn ^b   Rettkowski, Maria ^b   Frensing, Timo ^a   Reichl, Udo ^a,b  

^a MAX PLANCK INSTITUTE FOR DYNAMICS OF COMPLEX TECHNICAL SYSTEMS   (Germany)

^b OTTO VON GUERICKE UNIVERSITY   (Germany)

Author keywords

Influenza; Interferon; MDCK cells; Trypsin; Vaccine production

Indexed keywords

APOPTOSIS INDUCTION; CELLULAR RESPONSE; DEFENCE MECHANISMS; FETAL CALF SERUMS; HIGH YIELD; HOST CELLS; HOST RESPONSE; INFLUENZA; INFLUENZA VACCINES; INFLUENZA VIRUS; LOW LEVEL; MADIN-DARBY CANINE KIDNEY CELLS; MDCK CELLS; MULTI-CYCLE; OPTIMAL CONDITIONS; OVER-EXPRESSION; PROTEOLYTIC ACTIVATION; PROTEOLYTIC DEGRADATION; TRYPSIN; VACCINE PRODUCTION; VIRUS INFECTION; VIRUS REPLICATION; VIRUS SPREADING;

ANTIBIOTICS; CELL CULTURE; CELL DEATH; DEGRADATION; GLYCOPROTEINS; VACCINES;

VIRUSES;

INFLUENZA VACCINE; INTERFERON; TRYPSIN; VIRUS PHOSPHOPROTEIN;

APOPTOSIS; CYTOLOGY; INFLUENZA; INHIBITION; SECRETION; SERUM; VACCINE; VIRUS;

ANIMAL CELL; APOPTOSIS; ARTICLE; CELL STRAIN; CONTROLLED STUDY; HOST CELL; IMMUNE RESPONSE; INFLUENZA VIRUS; NONHUMAN; PROTEIN DEGRADATION; SIGNAL TRANSDUCTION; VACCINE PRODUCTION; VIRUS REPLICATION; VIRUS TITRATION; VIRUS VIRULENCE;

ANIMALS; ANTIVIRAL AGENTS; BIOTECHNOLOGY; CELL CULTURE TECHNIQUES; CELL LINE; DOGS; INFLUENZA VACCINES; INTERFERONS; ORTHOMYXOVIRIDAE; TECHNOLOGY, PHARMACEUTICAL; TRYPSIN;

ORTHOMYXOVIRIDAE; RABIES VIRUS; SUS;

EID: 84856287312     PISSN: 01757598     EISSN: 14320614     Source Type: Journal    
DOI: 10.1007/s00253-011-3569-8     Document Type: Article

References (58)

1. Arnheiter H, Haller O (1983) Mx gene control of interferon action: different kinetics of the antiviral state against influenza virus and vesicular stomatitis virus. J Virol 47(3):626-630 (Pubitemid 13033695)
2. Audsley JM, Tannock GA (2008) Cell-based influenza vaccines: progress to date. Drugs 68(11):1483-1491 (Pubitemid 352001186)
3. Balachandran S, Roberts PC, Kipperman T, Bhalla KN, Compans RW, Archer DR, Barber GN (2000) Alpha/beta interferons potentiate virus-induced apoptosis through activation of the FADD/caspase-8 death signaling pathway. J Virol 74(3):1513-1523 (Pubitemid 30044102)
4. Couch RB (2008) Seasonal inactivated influenza virus vaccines. Vaccine 26(Suppl 4):D5-D9
5. Doroshenko A, Halperin SA (2009) Trivalent MDCK cell culture-derived influenza vaccine Optaflu (Novartis Vaccines). Expert Rev Vaccines 8(6):679-688
6. Egorov A, Brandt S, Sereinig S, Romanova J, Ferko B, Katinger D, Grassauer A, Alexandrova G, Katinger H, Muster T (1998) Transfectant influenza A viruses with long deletions in the NS1 protein grow efficiently in Vero cells. J Virol 72(8):6437-6441 (Pubitemid 28323956)
7. Frensing T, Seitz C, Heynisch B, Patzina C, Kochs, G, Reichl, U (2011) Efficient influenza B virus propagation due to deficient interferon-induced antiviral activity in MDCK cells. Vaccine 29:7125-7129
8. García-Sastre A, Egorov A, Matassov D, Brandt S, Levy DE, Durbin JE, Palese P, Muster T (1998) Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems. Virology 252(2):324-330 (Pubitemid 29013414)
9. Gaush CR, Smith TF (1968) Replication and plaque assay of influenza virus in an established line of canine kidney cells. Appl Microbiol 16(4):588-594
10. Genzel Y, Reichl U (2009) Continuous cell lines as a production system for influenza vaccines. Expert Rev Vaccines 8(12):1681-1692
11. Genzel Y, Fischer M, Reichl U (2006) Serum-free influenza virus production avoiding washing steps and medium exchange in large-scale microcarrier culture. Vaccine 24(16):3261-3272
12. 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):461-475
13. Grimm D, Staeheli P, Hufbauer M, Koerner I, Martínez-Sobrido L, Solórzano A, García-Sastre A, Haller O, Kochs G (2007) Replication fitness determines high virulence of influenza A virus in mice carrying functional Mx1 resistance gene. Proc Natl Acad Sci USA 104(16):6806-6811 (Pubitemid 47175582)
14. Hale BG, Randall RE, Ortin J, Jackson D (2008) The multifunctional NS1 protein of influenza A viruses. J Gen Virol 89(Pt 10):2359-2376
15. Hale BG, Albrecht RA, García-Sastre A (2010) Innate immune evasion strategies of influenza viruses. Future Microbiol 5:23-41
16. Haller O, Staeheli P, Kochs G (2009) Protective role of interferon-induced Mx GTPases against influenza viruses. Rev Sci Tech 28(1):219-231
17. Hayman A, Comely S, Lackenby A, Murphy S, McCauley J, Goodbourn S, Barclay W (2006) Variation in the ability of human influenza A viruses to induce and inhibit the IFN-beta pathway. Virology 347(1):52-64
18. Hayman A, Comely S, Lackenby A, Hartgroves LCS, Goodbourn S, McCauley JW, Barclay WS (2007) NS1 proteins of avian influenza A viruses can act as antagonists of the human alpha/beta interferon response. J Virol 81(5):2318-2327
19. Heynisch B, Frensing T, Heinze K, Seitz C, Genzel Y, Reichl U (2010) Differential activation of host cell signalling pathways through infection with two variants of influenza A/Puerto Rico/8/34 (H1N1) in MDCK cells. Vaccine 28(51):8210-8218
20. Holzinger D, Jorns C, Stertz S, Boisson-Dupuis S, Thimme R, Weidmann M, Casanova JL, Haller O, Kochs G (2007) Induction of MxA gene expression by influenza A virus requires type I or type III interferon signaling. J Virol 81(14):7776-7785 (Pubitemid 47047864)
21. Honda K, Taniguchi T (2006) IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat Rev Immunol 6(9):644-658 (Pubitemid 44298214)
22. 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):5736-5740
23. 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):3848-3855
24. Iglewicz B (2000) Robust scale estimators and confidence intervals for location. Understanding robust and exploratory data analysis. D. C. Hoaglin. New York, Wiley: 404-432.
25. Isaacs A, Burke DC (1959) Viral interference and interferon. Br Med Bull 15:185-188
26. Jia D, Rahbar R, Chan RW, Lee SM, Chan MC, Wang BX, Baker DP, Sun B, Peiris JS, Nicholls JM, Fish EN (2010) Influenza virus non-structural protein 1 (NS1) disrupts interferon signaling. PLoS One 5(11):e13927
27. Kalbfuss B, Knochlein 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 (Pubitemid 351508423)
28. Kekarainen T, Martinez-Guino L, Segales J (2009) Swine torque teno virus detection in pig commercial vaccines, enzymes for laboratory use and human drugs containing components of porcine origin. J Gen Virol 90(Pt 3):648-653
29. Klenk HD, Rott R, Orlich M, Blodorn J (1975) Activation of influenza A viruses by trypsin treatment. Virology 68(2):426-439
30. Koerner I, Kochs G, Kalinke U, Weiss S, Staeheli P (2007) Protective role of beta interferon in host defense against influenza A virus. J Virol 81(4):2025-2030 (Pubitemid 46214473)
31. Lazarowitz SG, Choppin PW (1975) Enhancement of the infectivity of influenza A and B viruses by proteolytic cleavage of the hemagglutinin polypeptide. Virology 68(2):440-454
32. Lazarowitz SG, Goldberg AR, Choppin PW (1973) Proteolytic cleavage by plasmin of the HA polypeptide of influenza virus: host cell activation of serum plasminogen. Virology 56(1):172-180
33. 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):3661-3671
34. LeBouder F, Morello E, Rimmelzwaan GF, Bosse F, Pechoux C, Delmas B, Riteau B (2008) Annexin II incorporated into influenza virus particles supports virus replication by converting plasminogen into plasmin. J Virol 82(14):6820-6828 (Pubitemid 351977703)
35. Leyssen P, De Clercq E, Neyts J (2008) Molecular strategies to inhibit the replication of RNA viruses. Antiviral Res 78(1):9-25
36. Li IW, Chan KH, To KW, Wong SS, Ho PL, Lau SK, Woo PC, Tsoi HW, Chan JF, Cheng VC, Zheng BJ, Chen H, Yuen KY (2009) Differential susceptibility of different cell lines to swine-origin influenza A H1N1, seasonal human influenza A H1N1, and avian influenza A H5N1 viruses. J Clin Virol 46(4):325-330
37. Liu J, Shi X, Schwartz R, Kemble G (2009) Use of MDCK cells for production of live attenuated influenza vaccine. Vaccine 27(46):6460-6463
38. Makizumi K, Kimachi K, Fukada K, Nishimura T, Kudo Y, Goto S, Odagiri T, Tashiro M, Kino Y (2008) Timely production of A/Fujian-like influenza vaccine matching the 2003-2004 epidemic strain may have been possible using Madin-Darby canine kidney cells. Vaccine 26(52):6852-6858
39. Merten OW (2000) Safety for vaccine(e)s. Cytotechnology 34(3):181-183 (Pubitemid 32235011)
40. Noma K, Kiyotani K, Kouchi H, Fujii Y, Egi Y, Tanaka K, Yoshida T (1998) Endogenous protease-dependent replication of human influenza viruses in two MDCK cell lines. Arch Virol 143(10):1893-1909 (Pubitemid 28537093)
41. 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(17-19):2716-2721 (Pubitemid 32234294)
42. Pauli EK, Schmolke M, Wolff T, Viemann D, Roth J, Bode JG, Ludwig S (2008) Influenza A virus inhibits type I IFN signaling via NF-kappaB-dependent induction of SOCS-3 expression. PLoS Pathog 4(11):e1000196
43. Qiao L, Phipps-Yonas H, Hartmann B, Moran TM, Sealfon SC, Hayot F (2010) Immune response modeling of interferon beta-pretreated influenza virus-infected human dendritic cells. Biophys J 98(4):505-514
44. Randall RE, Goodbourn S (2008) Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J Gen Virol 89:1-47
45. Rieder M, Conzelmann KK (2009) Rhabdovirus evasion of the interferon system. J Interferon Cytokine Res 29(9):499-509
46. Romanova J, Krenn BM, Wolschek M, Ferko B, Romanovskaja-Romanko E, et al. (2009) Preclinical evaluation of a replication-deficient Intranasal ΔNS1 H5N1 influenza vaccine. PLoS ONE 4(6):e5984. doi: 10.1371/journal.pone.0005984
47. Schulze-Horsel J, Schulze M, Agalaridis G, Genzel Y, Reichl U (2009) Infection dynamics and virus-induced apoptosis in cell culture-based influenza vaccine production-flow cytometry and mathematical modeling. Vaccine 27(20):2712-2722
48. Schwarzer J, Rapp E, Reichl U (2008) N-glycan analysis by CGE-LIF: profiling influenza A virus hemagglutinin N-glycosylation during vaccine production. Electrophoresis 29(20):4203-4214
49. Seitz C, Frensing T, Höper D, Kochs G, Reichl U (2010) High yields of influenza A virus in Madin-Darby canine kidney cells are promoted by an insufficient interferon-induced antiviral state. J Gen Virol 91(Pt 7):1754-1763
50. Talon J, Horvath CM, Polley R, Basler CF, Muster T, Palese P, García-Sastre A (2000) Activation of interferon regulatory factor 3 is inhibited by the influenza A virus NS1 protein. J Virol 74(17):7989-7996 (Pubitemid 30641643)
51. Tobita K, Sugiura A, Enomote C, Furuyama M (1975) Plaque assay and primary isolation of influenza A viruses in an established line of canine kidney cells (MDCK) in the presence of trypsin. Med Microbiol Immunol 162(1):9-14
52. Tree JA, Richardson C, Fooks AR, Clegg JC, Looby D (2001) Comparison of large-scale mammalian cell culture systems with egg culture for the production of influenza virus A vaccine strains. Vaccine 19(25-26):3444-3450 (Pubitemid 32710294)
53. Ueda M, Yamate M, Du A, Daidoji T, Okuno Y, Ikuta K, Nakaya T (2008) Maturation efficiency of viral glycoproteins in the ER impacts the production of influenza A virus. Virus Res 136(1-2):91-97
54. Wang Z, Robb NC, Lenz E, Wolff T, Fodor E, Pleschka S (2010) NS reassortment of an H7-type highly pathogenic avian influenza virus affects its propagation by altering the regulation of viral RNA production and antiviral host response. J Virol 84(21):11323-11335
55. Willems E, Leyns L, Vandesompele J (2008) Standardization of real-time PCR gene expression data from independent biological replicates. Anal Biochem 379(1):127-129
56. Yamaoka M, Homma M, Hotta H (1995) MDCK cell cultures supplemented with high concentrations of trypsin exhibit remarkable susceptibility to influenza C virus. Arch Virol 140(5):937-944
57. Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, Taira K, Akira S, Fujita T (2004) The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol 5(7):730-737 (Pubitemid 39023305)
58. Young DF, Galiano MC, Lemon K, Chen YH, Andrejeva J, Duprex WP, Rima BK, Randall RE (2009) Mumps virus Enders strain is sensitive to interferon (IFN) despite encoding a functional IFN antagonist. J Gen Virol 90(Pt 11):2731-2738