Continuous cell lines as a production system for influenza vaccines

Expert Review of Vaccines

Volumn 8, Issue 12, 2009, Pages 1681-1692

  Genzel, Yvonne ^a   Reichl, Udo ^a,b  

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

^b OTTO VON GUERICKE UNIVERSITY   (Germany)

Author keywords

Adherent; AGE1.CR ; Continuous cell line; Influenza virus; MDCK; PER.C6 ; Suspension; Vaccine production; Vero

Indexed keywords

INFLUENZA VACCINE;

A549 CELL; AGE1 CR CELL; CELL CULTURE; CELL LINE; CELL STRAIN; CHICKEN; CLINICAL TRIAL; EGG; HOST CELL; HUMAN; INFLUENZA VIRUS A H5N1; LICENCE; MULTICENTER STUDY; NONHUMAN; PANDEMIC; PER C6 CELL; PRIORITY JOURNAL; REVIEW; VACCINE PRODUCTION; VERO CELL; VIRUS STRAIN;

ANIMALS; CELL CULTURE TECHNIQUES; CELL LINE; CERCOPITHECUS AETHIOPS; CLINICAL TRIALS AS TOPIC; DOGS; DRUG APPROVAL; HUMANS; INFLUENZA A VIRUS, H1N1 SUBTYPE; INFLUENZA VACCINES; INFLUENZA, HUMAN; KIDNEY; RETINA; VERO CELLS;

EID: 73849115748     PISSN: 14760584     EISSN: 17448395     Source Type: Journal    
DOI: 10.1586/erv.09.128     Document Type: Review

References (75)

1. Gerdil C. The annual production cycle for influenza vaccine. Vaccine 21(16), 1776-1779 (2003).
2. Wood JM, Levandowski RA. The influenza vaccine licensing process. Vaccine 21(16), 1786-1788 (2003).
3. Osterhaus AD. Pre- or post-pandemic influenza vaccine? Vaccine 25(27), 4983-4984 (2007).
4. Hu AY, Weng TC, Tseng YF et al. Microcarrier-based MDCK cell culture system for the production of influenza H5N1 vaccines. Vaccine 26(45), 5736-5740 (2008). • Latest details on the Vero production process from Baxter Vaccines (Vienna, Austria).
5. Howard MK, Kistner O, Barrett PN. Pre-clinical development of cell culture (Vero)-derived H5N1 pandemic vaccines. Biol. Chem. 389(5), 569-577 (2008).
6. Horimoto T, Kawaoka Y. Strategies for developing vaccines against H5N1 influenza A viruses. Trends Mol. Med. 12(11), 506-514 (2006).
7. Ozawa M, Goto H, Horimoto T, Kawaoka Y. An adenovirus vector-mediated reverse genetics system for influenza A virus generation. J. Virol. 81(17), 9556-9559 (2007).
8. Gabriel G, Garn H, Wegmann M et al. The potential of a protease activation mutant of a highly pathogenic avian influenza virus for a pandemic live vaccine. Vaccine 26(7), 956-965 (2008).
9. Kemble G, Greenberg H. Novel generations of influenza vaccines. Vaccine 21(16), 1789-1795 (2003).
10. Lohr V, Rath A, Genzel Y, Jordan I, Sandig V, Reichl U. 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), 4975-4982 (2009).
11. Jordan I, Vos A, Beilfuss S, Neubert A, Breul S, Sandig V. An avian cell line designed for production of highly attenuated viruses. Vaccine 27(5), 748-756 (2009).
12. Cox MM, Hollister JR. FluBlok, a next generation influenza vaccine manufactured in insect cells. Biologicals 37(3), 182-189 (2009).
13. Palese P. Making better influenza virus vaccines? Emerg. Infect. Dis. 12(1), 61-65 (2006).
14. Makizumi K, Kimachi K, Fukada K et al. 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 (2008).
15. Minor PD, Engelhardt OG, Wood JM et al. Current challenges in implementing cell-derived influenza vaccines: implications for production and regulation, July 2007, NIBSC, Potters Bar, UK. Vaccine 27(22), 2907-2913 (2009).
16. Nicolson C, Major D, Wood JM, Robertson JS. Generation of influenza vaccine viruses on Vero cells by reverse genetics: an H5N1 candidate vaccine strain produced under a quality system. Vaccine 23(22), 2943-2952 (2005).
17. Palker T, Kiseleva I, Johnston K et al. Protective efficacy of intranasal coldadapted influenza A/New Caledonia/20/99 (H1N1) vaccines comprised of egg- or cell culture-derived reassortants. Virus Res. 105(2), 183-194 (2004).
18. Ambrose CS, Luke C, Coelingh K. Current status of live attenuated influenza vaccine in the United States for seasonal and pandemic influenza. Influenza Other Respi. Viruses 2(6), 193-202 (2008).
19. Rudenko L, Desheva J, Korovkin S et al. Safety and immunogenicity of live attenuated influenza reassortant H5 vaccine (Phase I-II clinical trials). Influenza Other Respi. Viruses 2(6), 203-209 (2008).
20. Aunins JG. Viral vaccine production in cell culture. In: Encyclopedia of Cell Technology. Spier RE (Ed.). Wiley & Sons, NY, USA, 1182-1217 (2000).
21. Lubiniecki AS. Continuous cell substrate considerations. Bioprocess Technol. 10, 495-513 (1990).
22. WHO. Cell culture as a substrate for the production of influenza vaccines: memorandum from a WHO meeting. Bull. World Health Organ.. 73, 431-435 (1995).
23. Madin SH, Darby NB Jr. Established kidney cell lines of normal adult bovine and ovine origin. Proc. Soc. Exp. Biol. Med. 98(3), 574-576 (1958).
24. Cordat E. Unraveling trafficking of the kidney anion exchanger 1 in polarized MDCK epithelial cells. Biochem. Cell Biol. 84(6), 949-959 (2006).
25. Simmons NL. Cultured monolayers of MDCK cells: a novel model system for the study of epithelial development and function. Gen. Pharmacol. 13(4), 287-291 (1982).
26. Tree JA, Richardson C, Fooks AR, Clegg JC, Looby D. 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 (2001).
27. Rimmelzwaan GF, Baars M, Claas EC, Osterhaus AD. Comparison of RNA hybridization, hemagglutination assay, titration of infectious virus and immunofluorescence as methods for monitoring influenza virus replication in vitro. J. Virol. Methods 74(1), 57-66 (1998).
28. Doroshenko A, Halperin SA. Trivalent MDCK cell culture-derived influenza vaccine Optaflu® (Novartis vaccines). Expert Rev. Vaccines 8(6), 679-688 (2009).
29. Genzel Y, Behrendt I, Konig S, Sann H, Reichl U. Metabolism of MDCK cells during cell growth and influenza virus production in large-scale microcarrier culture. Vaccine 22(17-18), 2202-2208 (2004).
30. Liu J, Shi X, Schwartz R, Kemble G. Use of MDCK cells for production of live attenuated influenza vaccine. Vaccine 27(46), 6460-6463 (2009).
31. Genzel Y, Fischer M, Reichl U. Serum-free influenza virus production avoiding washing steps and medium exchange in large-scale microcarrier culture. Vaccine 24(16), 3261-3272 (2006).
32. Genzel Y, Olmer RM, Schafer B, Reichl U. Wave microcarrier cultivation of MDCK cells for influenza virus production in serum containing and serum-free media. Vaccine 24(35-36), 6074-6087 (2006).
33. Bock A, Reichl U. Closed loop control of perfusion systems in high-density cell culture. In: Cell Technology for Cell Products, 19th ESACT Meeting. Smith R (Ed.). Springer, Harrogate, UK, 549-551 (2005).
34. Schulze-Horsel J, Schulze M, Agalaridis G, Genzel Y, Reichl U. Infection dynamics and virus-induced apoptosis in cell culturebased influenza vaccine production - flow cytometry and mathematical modeling. Vaccine 27(20), 2712-2722 (2009).
35. Palache AM, Brands R, van Scharrenburg GJ. Immunogenicity and reactogenicity of influenza subunit vaccines produced in MDCK cells or fertilized chicken eggs. J. Infect. Dis. 176(Suppl. 1), S20-S23 (1997).
36. Gregersen JP. A quantitative risk assessment of exposure to adventitious agents in a cell culture-derived subunit influenza vaccine. Vaccine 26(26), 3332-3340 (2008).
37. Gregersen JP. A risk-assessment model to rate the occurrence and relevance of adventitious agents in the production of influenza vaccines. Vaccine 26(26), 3297-3304 (2008).
38. Groth N, Montomoli E, Gentile C, Manini I, Bugarini R, Podda A. Safety, tolerability and immunogenicity of a mammalian cell-culture-derived influenza vaccine: a sequential Phase I and Phase II clinical trial. Vaccine 27(5), 786-791 (2009).
39. Polymenidou M, Trusheim H, Stallmach L et al. Canine MDCK cell lines are refractory to infection with human and mouse prions. Vaccine 26(21), 2601-2614 (2008).
40. Halperin SA, Smith B, Mabrouk T et al. Safety and immunogenicity of a trivalent, inactivated, mammalian cell culturederived influenza vaccine in healthy adults, seniors, and children. Vaccine 20(7-8), 1240-1247 (2002).
41. Reisinger KS, Block SL, Izu A, Groth N, Holmes SJ. Subunit influenza vaccines produced from cell culture or in embryonated chicken eggs: comparison of safety, reactogenicity, and immunogenicity. J. Infect. Dis. 200(6), 849-857 (2009).
42. Oh DY, Barr IG, Mosse JA, Laurie KL. MDCK-SIAT1 cells show improved isolation rates for recent human influenza viruses compared to conventional MDCK cells. J. Clin. Microbiol. 46(7), 2189-2194 (2008).
43. Murakami S, Horimoto T, Mai LQ et al. Growth determinants for H5N1 influenza vaccine seed viruses in MDCK cells. J. Virol. 82(21), 10502-10509 (2008).
44. Murakami S, Horimoto T, Yamada S, Kakugawa S, Goto H, Kawaoka Y. Establishment of canine RNA polymerase I-driven reverse genetics for influenza A virus: its application for H5N1 vaccine production. J. Virol. 82(3), 1605-1609 (2008).
45. Wang Z, Duke GM. Cloning of the canine RNA polymerase I promoter and establishment of reverse genetics for influenza A and B in MDCK cells. Virol. J. 4, 102 (2007).
46. Trabelsi K, Rourou S, Loukil H, Majoul S, Kallel H. Optimization of virus yield as a strategy to improve rabies vaccine production by Vero cells in a bioreactor. J. Biotechnol. 121(2), 261-271 (2006).
47. Rourou S, van der Ark A, van der Velden T, Kallel H. A microcarrier cell culture process for propagating rabies virus in Vero cells grown in a stirred bioreactor under fully animal component free conditions. Vaccine 25(19), 3879-3889 (2007).
48. Barrett PN, Mundt W, Kistner O, Howard MK. Vero cell platform in vaccine production: moving towards cell culturebased viral vaccines. Expert Rev. Vaccines 8(5), 607-618 (2009).
49. Youil R, Su Q, Toner TJ et al. Comparative study of influenza virus replication in Vero and MDCK cell lines. J. Virol Methods 120(1), 23-31 (2004).
50. Wu SC, Huang GYL. Hydrodynamic shear forces increase Japanese encephalitis virus production from microcarrier-grown Vero cells. Bioprocess Engineering 23(3), 229-233 (2000).
51. Wu SC. Influence of hydrodynamic shear stress on microcarrier-attached cell growth: cell line dependency and surfactant protection. Bioprocess Engineering 21(3), 201-206 (1999).
52. Kistner O, Howard MK, Spruth M et al. Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses. Vaccine 25(32), 6028-6036 (2007).
53. Desmyter J, Melnick JL, Rawls WE. Defectiveness of interferon production and of rubella virus interference in a line of African green monkey kidney cells (Vero). J. Virol. 2(10), 955-961 (1968).
54. Schwarzer J, Rapp E, Hennig R et al. Glycan analysis in cell culture-based influenza vaccine production: influence of host cell line and virus strain on the glycosylation pattern of viral hemagglutinin. Vaccine 27(32), 4325-4336 (2009).
55. Opitz L, Salaklang J, Buttner H, Reichl U, Wolff MW. Lectin-affinity chromatography for downstream processing of MDCK cell culture derived human influenza A viruses. Vaccine 25(5), 939-947 (2007).
56. Nishiyama K, Sugawara K, Nouchi T et al. Purification and cDNA cloning of a novel protease inhibitor secreted into culture supernatant by MDCK cells. Biologicals 36(2), 122-133 (2008).
57. Kaverin NV, Webster RG. Impairment of multicycle influenza virus growth in Vero (WHO) cells by loss of trypsin activity. J. Virol. 69(4), 2700-2703 (1995).
58. Kistner O, Barrett PN, Mundt W, Reiter M, Schober-Bendixen S, Dorner F. Development of a mammalian cell (Vero) derived candidate influenza virus vaccine. Vaccine 16(9-10), 960-968 (1998).
59. Ehrlich HJ, Muller M, Fritsch S et al. A cell culture (Vero)-derived H5N1 whole-virus vaccine induces cross-reactive memory responses. J. Infect. Dis. 200(7), 1113-1118 (2009).
60. Ueda M, Yamate M, Du A et al. Maturation efficiency of viral glycoproteins in the ER impacts the production of influenza A virus. Virus Res. 136(1-2), 91-97 (2008).
61. Marjuki H, Scholtissek C, Yen HL, Webster RG. CK2b gene silencing increases cell susceptibility to influenza A virus infection resulting in accelerated virus entry and higher viral protein content. J. Mol. Signal. 3, 13 (2008).
62. Bradel-Tretheway BG, Kelley Z, Chakraborty-Sett S, Takimoto T, Kim B, Dewhurst S. The human H5N1 influenza A virus polymerase complex is active in vitro over a broad range of temperatures, in contrast to the WSN complex, and this property can be attributed to the PB2 subunit. J. Gen. Virol. 89(Pt 12), 2923-2932 (2008).
63. Daidoji T, Koma T, Du A et al. H5N1 avian influenza virus induces apoptotic cell death in mammalian airway epithelial cells. J. Virol. 82(22), 11294-11307 (2008).
64. Vester D, Rapp E, Gade D, Genzel Y, Reichl U. Quantitative analysis of cellular proteome alterations in human influenza A virus-infected mammalian cell lines. Proteomics 9(12), 3316-3327 (2009).
65. Fallaux FJ, Bout A, van der Velde I et al. New helper cells and matched early region 1-deleted adenovirus vectors prevent generation of replication-competent adenoviruses. Hum. Gene Ther. 9(13), 1909-1917 (1998).
66. Pau MG, Ophorst C, Koldijk MH, Schouten G, Mehtali M, Uytdehaag F. The human cell line PER.C6 provides a new manufacturing system for the production of influenza vaccines. Vaccine 19(17-19), 2716-2721 (2001). • Details of the use of PER.C6® for influenza vaccine production.
67. Cox RJ, Madhun AS, Hauge S et al. A Phase I clinical trial of a PER.C6 cell grown influenza H7 virus vaccine. Vaccine 27(13), 1889-1897 (2009).
68. Koudstaal W, Hartgroves L, Havenga M et al. Suitability of PER.C6 cells to generate epidemic and pandemic influenza vaccine strains by reverse genetics. Vaccine 27(19), 2588-2593 (2009).
69. Berdichevsky M, Gentile MP, Hughes B et al. Establishment of higher passage PER. C6 cells for adenovirus manufacture. Biotechnol. Prog. 24(1), 158-165 (2008).
70. Smith KA, Colvin CJ, Weber PS, Spatz SJ, Coussens PM. High titer growth of human and avian influenza viruses in an immortalized chick embryo cell line without the need for exogenous proteases. Vaccine 26(29-30), 3778-3782 (2008).
71. Seo SH, Goloubeva O, Webby R, Webster RG. Characterization of a porcine lung epithelial cell line suitable for influenza virus studies. J. Virol. 75(19), 9517-9525 (2001).
72. Ogura H, Fujiwara T. Establishment and characterization of a virus-free chick cell-line. Acta Medica Okayama 41(3), 141-143 (1987).
73. Audsley JM, Tannock GA. The growth of attenuated influenza vaccine donor strains in continuous cell lines. J. Virol. Methods 123(2), 187-193 (2005).
74. Mendonca RZ, Arrozio SJ, Antoniazzi MM, Ferreira JM Jr, Pereira CA. Metabolic active-high density VERO cell cultures on microcarriers following apoptosis prevention by galactose/ glutamine feeding. J. Biotechnol. 97(1), 13-22 (2002).
75. Quesney S, Marc A, Gerdil C et al. Kinetics and metabolic specificities of Vero cells in bioreactor cultures with serum-free medium. Cytotechnology 42(1), 1-11 (2003).