Comparison of large-scale mammalian cell culture systems with egg culture for the production of influenza virus A vaccine strains

Tree, Julia A.; Richardson, Catherine; Fooks, Anthony R.; Clegg, J. C. S.; Looby, Denis

doi:10.1016/s0264-410x(01)00053-6

Cited by 143 publications

(111 citation statements)

References 12 publications

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“…Influenza virus is currently being produced in embryonated eggs (27). Since the production in eggs is quite cumbersome and time consuming, replacing the embryonated eggs process with mammalian cells, especially MDCK cells, is an appealing option (4,6,8). Since MDCK cells are anchorage-dependent, the replacement of the embryonated eggs with these cells will introduce additional processing difficulty.…”

Section: Discussionmentioning

confidence: 99%

“…Among the potential alternatives for vaccine production, the use of characterized, immortalized cell lines (particularly MDCK, VERO, and PER.C6) has been investigated. These cell lines have been found to produce consistently high viral titers (3)(4)(5)(6)(7)(8). Nevertheless, one of the limiting aspects in scaling up the virus production in these continuous cell lines is the fact that these cells are anchorage-dependent and thus require surface adhesion to proliferate (9,10).…”

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confidence: 99%

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Conversion of MDCK cell line to suspension culture by transfecting with human siat7e gene and its application for influenza virus production

Chu

Lugovtsev

Golding

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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MDCK cells are currently being considered as an alternative to embryonated eggs for influenza virus propagation and hemagglutinin (HA) production intended for vaccine manufacturing. MDCK cells were found suitable for the virus production but their inability to grow in suspension burdens the process of scale up and hence their production capability. Anchorage-dependent MDCK cells were converted to anchorage-independent cells, capable of growing in suspension as a result of transfection with the human siat7e gene (ST6GalNac V). This gene was previously identified as having an important role in cellular adhesion when the transcriptions of genes from anchorage-dependent and anchorage-independent HeLa cells were compared. Unlike the parental MDCK cells, the siat7e-expressing cells were capable of growing in shake flasks as suspension cultures, achieving maximum concentration of 7 ؋ 10 5 cells/mL while keeping close to 100% viability throughout the growth phase. In production experiments, the siat7e-expressing cells were infected with the Influenza B/Victoria/504/2000 strain. It was determined that the cell-derived viruses retained similar antigenic properties as those obtained from egg-derived viruses and their nucleotide sequences were identical. The specific production of hemagglutinin (expressed in hemagglutination units per 10 6 cells) from the siat7e-expressing cells was approximately 20 times higher than the specific production from the parental MDCK cells. If this suspension process scales up, the production potential of HA from 10 L of siat7e-expressing cells at a concentration of 10 6 cells/mL would be equivalent to the amount of HA obtained from 10,000 embryonated eggs.anchorage-independent ͉ hemagglutinin ͉ sialyltransferase ͉ vaccine

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Conversion of MDCK cell line to suspension culture by transfecting with human siat7e gene and its application for influenza virus production

Chu

Lugovtsev

Golding

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…The cells can be easily adapted to and be grown in serum-free media, and in suspension, as well as on various microcarriers maintained under various bioreactor conditions. 93,[101][102][103][104][105][106][107][108] Subclones of MDCK cells adopted to grow in suspension and support robust virus production have also been described, 91,108,109 although adherent MDCK cells appear to support more robust virus production than suspension MDCK cells. 110 Influenza vaccines derived from MDCK cells are also safe and immunogenic.…”

Section: Mdck Cell-derived Influenza Vaccines: the Final Joust?mentioning

confidence: 99%

Cell culture-based influenza vaccines: A necessary and indispensable investment for the future

Hegde

2015

Human Vaccines & Immunotherapeutics

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“…11,12 Egg culture remains the most efficient large-scale production system for influenza A vaccine as compared to various mammalian cell culture systems. 14 The results of recent studies, which show the absence of adverse effects in vaccinees, underscore the safety of this production system. 13 One of major characteristics of an anticancer drug is its efficacy.…”

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confidence: 94%

Avian adenovirus vector CELO-TK displays anticancer activity in human cancer cells and suppresses established murine melanoma tumors

et al. 2005

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Avian adenovirus CELO is a novel adenovirus vector system with the advantages of efficient production, high virion stability, and the absence of crossreactivity with Ad5-neutralizing antibodies. In this study, we evaluated the anticancer efficacy of a CELO vector encoding the herpes simplex virus type 1 thymidine kinase, a prodrug-activating therapeutic gene. Vectors carrying the gene for HSV-tk or EGFP under the control of the HCMV promoter in place of the ''nonessential'' region of the CELO genome were constructed. Anticancer activity of the CELO-TK vector was studied in vitro, in human and murine tumor cells in cell culture, and in vivo, in established subcutaneous murine B16 melanoma tumors in C57BL/6 mice. The CELO-TK vector mediated delivery of functional HSV-tk to tumor cell lines in cell culture. Comparison of the CELO-TK vector to a first-generation human adenovirus type 5 vector Ad5-TK in cultured H1299 cells showed equal levels of functional activity at increasing multiplicities of infection with CELO-based vector. CELO vectors allowed for transduction and expression of EGFP and HSV-tk genes in subcutaneous melanoma tumors in C57BL/6 mice. Intratumoral injections of CELO-TK followed by ganciclovir administration resulted in suppression of tumor growth and significantly increased the median of survival. The results of the study demonstrated the efficacy of CELO vector as a vehicle for the delivery of prodrug-activating genes such as HSV-tk to tumor cells in vitro and in vivo. Cancer Gene Therapy ( 1 This experimental approach to cancer treatment is currently in a transition from promise to reality with recent approval of an adenovirus (Ad) vector expressing p53 for use in clinics and with many more vectors in late stages of clinical trials.2 At the same time, new generations of cancer gene therapy vectors are being developed that will provide higher levels of efficacy, specificity, and cost-effectiveness.Whereas human Ad type 5 (Ad5) is a common platform for Ad vectors for the in vitro and in vivo delivery of genes, 3,4 non-human adenoviruses (Ads), also referred to as ''xenogeneic'' vectors, are currently emerging as alternative or additional gene delivery vehicles. 5,6 Avian Ad CELO (FAV-1) is a novel non-human Ad vector that has potential advantages for the development of anticancer vectors including: (i) the absence of pre-existing immunity to CELO in the human population, 7 (ii) the absence of immunological crossreactivity between virions of Ad5 and CELO, 8 which allows for in vivo transduction by CELO vectors in the presence of anti-Ad5 neutralizing antibodies, 9 (iii) higher stability of CELO virions as compared to Ad5 virions, 7 (iv) the natural inability of CELO to replicate in non-avian cells, which renders CELO vectors gene delivery vehicles rather than replicative agents in mammalian cells, 7 (v) the ability of CELO vectors to grow in noncomplementing cells resulting in the absence of recombination with the homologous viral DNA sequences in the genome of a complementing cell line, and the a...

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Comparison of large-scale mammalian cell culture systems with egg culture for the production of influenza virus A vaccine strains

Cited by 143 publications

References 12 publications

Conversion of MDCK cell line to suspension culture by transfecting with human siat7e gene and its application for influenza virus production

Conversion of MDCK cell line to suspension culture by transfecting with human siat7e gene and its application for influenza virus production

Cell culture-based influenza vaccines: A necessary and indispensable investment for the future

Avian adenovirus vector CELO-TK displays anticancer activity in human cancer cells and suppresses established murine melanoma tumors

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