title: Comparison of immunogenicity of cell-and egg-passaged viruses for manufacturing MDCK cell culture-based influenza vaccines.
abstract: While cell culture-based technology has been recently used for manufacturing influenza vaccines, currently available seed viruses are mostly egg-derived reassortants that are egg-adapted to achieve high virus growth in eggs. For use as viruses for cell culture-based influenza vaccine manufacturing, egg-adapted viral seeds may undergo several passages in manufacturing cell lines. However, the suitability of such cell-passaged viruses for vaccine production remains largely unelucidated. In this study, influenza viruses produced in suspension Madin-Darby canine kidney (MDCK) cell cultures were compared to those produced in embryonated hen's eggs for manufacturing MDCK cell culture-based influenza vaccines through comparability studies of virus productivity and vaccine immunogenicity. The results indicate no change in the amino acid sequence of the main antigens, including hemagglutinin (HA) and neuraminidase (NA), of cell-passaged viruses after three passages in suspension MDCK cells. In lab-scale (3-L) single-use bioreactors, suspension MDCK culture supernatants inoculated with cell-passaged viruses were found to show higher virus productivity, suspension MDCK culture supernatants inoculated with egg-passaged viruses, in respect to the HA titers and HA contents determined by single radial immunodiffusion. Finally, comparable hemagglutination inhibition and influenza-specific IgG titers were determined in the mice immunized with cell culture-based vaccines produced with cell- or egg-passaged viruses. These results indicate that MDCK cell-passaged viruses from egg-adapted viruses, as well as egg-derived seed virus, are suitable for MDCK cell culture-based influenza vaccine production.
authors.affiliation: Vaccine, Mogam Biotechnology Research Institute, 107, Ihyeon-ro 30beon-gil, Giheung-gu, Yongin-si, Gyeonggi-do, Korea, 446-770, Republic of Korea; Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52, Ewhayeodae-gil, Seodaemun-gu, Seoul 120-750, Republic of Korea.
authors.forename: Duckhyang
authors.initials: D
authors.lastname: Shin
authors.affiliation: Virus Vaccine, Green Cross Research Center, 93, Ihyeon-ro 30beon-gil, Giheung-gu, Yongin-si, Gyeonggi-do, Korea, 446-850, Republic of Korea.
authors.forename: Kuk Jin
authors.initials: KJ
authors.lastname: Park
authors.affiliation: Vaccine, Mogam Biotechnology Research Institute, 107, Ihyeon-ro 30beon-gil, Giheung-gu, Yongin-si, Gyeonggi-do, Korea, 446-770, Republic of Korea.
authors.forename: Hyeon
authors.initials: H
authors.lastname: Lee
authors.affiliation: Virus Vaccine, Green Cross Research Center, 93, Ihyeon-ro 30beon-gil, Giheung-gu, Yongin-si, Gyeonggi-do, Korea, 446-850, Republic of Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Cho
authors.affiliation: Virus Vaccine, Green Cross Research Center, 93, Ihyeon-ro 30beon-gil, Giheung-gu, Yongin-si, Gyeonggi-do, Korea, 446-850, Republic of Korea.
authors.forename: Mi Suk
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Virus Vaccine, Green Cross Research Center, 93, Ihyeon-ro 30beon-gil, Giheung-gu, Yongin-si, Gyeonggi-do, Korea, 446-850, Republic of Korea.
authors.forename: Mi Hui
authors.initials: MH
authors.lastname: Hwang
authors.affiliation: Virus Vaccine, Green Cross Research Center, 93, Ihyeon-ro 30beon-gil, Giheung-gu, Yongin-si, Gyeonggi-do, Korea, 446-850, Republic of Korea.
authors.forename: Soo In
authors.initials: SI
authors.lastname: Kim
authors.affiliation: Virus Vaccine, Green Cross Research Center, 93, Ihyeon-ro 30beon-gil, Giheung-gu, Yongin-si, Gyeonggi-do, Korea, 446-850, Republic of Korea. Electronic address: dhahn@greencross.com.
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Ahn
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D018929:Cell Culture Techniques; D002645:Chickens / Q000276:immunology* / Q000821:virology; D004285:Dogs; D004531:Eggs; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006388:Hemagglutinins / Q000276:immunology; D006801:Humans; D007114:Immunization; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D009439:Neuraminidase / Q000276:immunology; D009975:Orthomyxoviridae / Q000276:immunology*; D014776:Virus Cultivation / Q000379:methods*
chemical_list: D000956:Antigens, Viral; D006388:Hemagglutinins; D007252:Influenza Vaccines; D009439:Neuraminidase
keywords: Cell culture influenza vaccine; Influenza; Suspension MDCK cell