Sars-cov-2 production in a scalable high cell density bioreactor

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Standard

Sars-cov-2 production in a scalable high cell density bioreactor. / Offersgaard, Anna; Hernandez, Carlos Rene Duarte; Pihl, Anne Finne; Costa, Rui; Venkatesan, Nandini Prabhakar; Lin, Xiangliang; Van Pham, Long; Feng, Shan; Fahnøe, Ulrik; Scheel, Troels Kasper Høyer; Ramirez, Santseharay; Reichl, Udo; Bukh, Jens; Genzel, Yvonne; Gottwein, Judith Margarete.

I: Vaccines, Bind 9, Nr. 7, 706, 2021.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Offersgaard, A, Hernandez, CRD, Pihl, AF, Costa, R, Venkatesan, NP, Lin, X, Van Pham, L, Feng, S, Fahnøe, U, Scheel, TKH, Ramirez, S, Reichl, U, Bukh, J, Genzel, Y & Gottwein, JM 2021, 'Sars-cov-2 production in a scalable high cell density bioreactor', Vaccines, bind 9, nr. 7, 706. https://doi.org/10.3390/vaccines9070706

APA

Offersgaard, A., Hernandez, C. R. D., Pihl, A. F., Costa, R., Venkatesan, N. P., Lin, X., Van Pham, L., Feng, S., Fahnøe, U., Scheel, T. K. H., Ramirez, S., Reichl, U., Bukh, J., Genzel, Y., & Gottwein, J. M. (2021). Sars-cov-2 production in a scalable high cell density bioreactor. Vaccines, 9(7), [706]. https://doi.org/10.3390/vaccines9070706

Vancouver

Offersgaard A, Hernandez CRD, Pihl AF, Costa R, Venkatesan NP, Lin X o.a. Sars-cov-2 production in a scalable high cell density bioreactor. Vaccines. 2021;9(7). 706. https://doi.org/10.3390/vaccines9070706

Author

Offersgaard, Anna ; Hernandez, Carlos Rene Duarte ; Pihl, Anne Finne ; Costa, Rui ; Venkatesan, Nandini Prabhakar ; Lin, Xiangliang ; Van Pham, Long ; Feng, Shan ; Fahnøe, Ulrik ; Scheel, Troels Kasper Høyer ; Ramirez, Santseharay ; Reichl, Udo ; Bukh, Jens ; Genzel, Yvonne ; Gottwein, Judith Margarete. / Sars-cov-2 production in a scalable high cell density bioreactor. I: Vaccines. 2021 ; Bind 9, Nr. 7.

Bibtex

@article{c8eb2e4d0a624ed39b2293db73e792cc,

title = "Sars-cov-2 production in a scalable high cell density bioreactor",

abstract = "The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has demonstrated the value of pursuing different vaccine strategies. Vaccines based on whole viruses, a widely used vaccine technology, depend on efficient virus production. This study aimed to establish SARSCoV-2 production in the scalable packed-bed CelCradle{\texttrademark} 500-AP bioreactor. CelCradle{\texttrademark} 500-AP bottles with 0.5 L working volume and 5.5 g BioNOC{\texttrademark} II carriers were seeded with 1.5 × 108 Vero (WHO) cells, approved for vaccine production, in animal component-free medium and infected at a multiplicity of infection of 0.006 at a total cell number of 2.2–2.5 × 109 cells/bottle seven days post cell seeding. Among several tested conditions, two harvests per day and a virus production temperature of 33◦C resulted in the highest virus yield with a peak SARS-CoV-2 infectivity titer of 7.3 log10 50% tissue culture infectious dose (TCID50)/mL at 72 h post-infection. Six harvests had titers of ≥6.5 log10 TCID50/mL, and a total of 10.5 log10 TCID50 were produced in ~5 L. While trypsin was reported to enhance virus spread in cell culture, addition of 0.5% recombinant trypsin after infection did not improve virus yields. Overall, we demonstrated successful animal component-free production of SARS-CoV-2 in well-characterized Vero (WHO) cells in a scalable packed-bed bioreactor.",

keywords = "Animal component-free, CelCradle, COVID-19, Inactivated vaccine, Packed-bed, Scalable bioreactor, Severe acute respiratory syndrome coronavirus 2, Vero cells, Whole virus vaccine",

author = "Anna Offersgaard and Hernandez, {Carlos Rene Duarte} and Pihl, {Anne Finne} and Rui Costa and Venkatesan, {Nandini Prabhakar} and Xiangliang Lin and {Van Pham}, Long and Shan Feng and Ulrik Fahn{\o}e and Scheel, {Troels Kasper H{\o}yer} and Santseharay Ramirez and Udo Reichl and Jens Bukh and Yvonne Genzel and Gottwein, {Judith Margarete}",

note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

doi = "10.3390/vaccines9070706",

language = "English",

volume = "9",

journal = "Vaccines",

issn = "2076-393X",

publisher = "MDPI AG",

number = "7",

}

RIS

TY - JOUR

T1 - Sars-cov-2 production in a scalable high cell density bioreactor

AU - Offersgaard, Anna

AU - Hernandez, Carlos Rene Duarte

AU - Pihl, Anne Finne

AU - Costa, Rui

AU - Venkatesan, Nandini Prabhakar

AU - Lin, Xiangliang

AU - Van Pham, Long

AU - Feng, Shan

AU - Fahnøe, Ulrik

AU - Scheel, Troels Kasper Høyer

AU - Ramirez, Santseharay

AU - Reichl, Udo

AU - Bukh, Jens

AU - Genzel, Yvonne

AU - Gottwein, Judith Margarete

PY - 2021

Y1 - 2021

N2 - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has demonstrated the value of pursuing different vaccine strategies. Vaccines based on whole viruses, a widely used vaccine technology, depend on efficient virus production. This study aimed to establish SARSCoV-2 production in the scalable packed-bed CelCradle™ 500-AP bioreactor. CelCradle™ 500-AP bottles with 0.5 L working volume and 5.5 g BioNOC™ II carriers were seeded with 1.5 × 108 Vero (WHO) cells, approved for vaccine production, in animal component-free medium and infected at a multiplicity of infection of 0.006 at a total cell number of 2.2–2.5 × 109 cells/bottle seven days post cell seeding. Among several tested conditions, two harvests per day and a virus production temperature of 33◦C resulted in the highest virus yield with a peak SARS-CoV-2 infectivity titer of 7.3 log10 50% tissue culture infectious dose (TCID50)/mL at 72 h post-infection. Six harvests had titers of ≥6.5 log10 TCID50/mL, and a total of 10.5 log10 TCID50 were produced in ~5 L. While trypsin was reported to enhance virus spread in cell culture, addition of 0.5% recombinant trypsin after infection did not improve virus yields. Overall, we demonstrated successful animal component-free production of SARS-CoV-2 in well-characterized Vero (WHO) cells in a scalable packed-bed bioreactor.

AB - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has demonstrated the value of pursuing different vaccine strategies. Vaccines based on whole viruses, a widely used vaccine technology, depend on efficient virus production. This study aimed to establish SARSCoV-2 production in the scalable packed-bed CelCradle™ 500-AP bioreactor. CelCradle™ 500-AP bottles with 0.5 L working volume and 5.5 g BioNOC™ II carriers were seeded with 1.5 × 108 Vero (WHO) cells, approved for vaccine production, in animal component-free medium and infected at a multiplicity of infection of 0.006 at a total cell number of 2.2–2.5 × 109 cells/bottle seven days post cell seeding. Among several tested conditions, two harvests per day and a virus production temperature of 33◦C resulted in the highest virus yield with a peak SARS-CoV-2 infectivity titer of 7.3 log10 50% tissue culture infectious dose (TCID50)/mL at 72 h post-infection. Six harvests had titers of ≥6.5 log10 TCID50/mL, and a total of 10.5 log10 TCID50 were produced in ~5 L. While trypsin was reported to enhance virus spread in cell culture, addition of 0.5% recombinant trypsin after infection did not improve virus yields. Overall, we demonstrated successful animal component-free production of SARS-CoV-2 in well-characterized Vero (WHO) cells in a scalable packed-bed bioreactor.

KW - Animal component-free

KW - CelCradle

KW - COVID-19

KW - Inactivated vaccine

KW - Packed-bed

KW - Scalable bioreactor

KW - Severe acute respiratory syndrome coronavirus 2

KW - Vero cells

KW - Whole virus vaccine

U2 - 10.3390/vaccines9070706

DO - 10.3390/vaccines9070706

M3 - Journal article

C2 - 34209694

AN - SCOPUS:85109955506

VL - 9

JO - Vaccines

JF - Vaccines

SN - 2076-393X

IS - 7

M1 - 706

ER -

ID: 275014136