Vero Cell Upstream Bioprocess Development for the Production of Viral Vectors and Vaccines

Overview

Journal Biotechnol Adv

Specialties Biochemistry
Biotechnology

Date 2020 Aug 10

PMID 32768520

Citations 51

Authors

Sascha Kiesslich

Amine A Kamen

Affiliations

Soon will be listed here.

Abstract

The Vero cell line is considered the most used continuous cell line for the production of viral vectors and vaccines. Historically, it is the first cell line that was approved by the WHO for the production of human vaccines. Comprehensive experimental data on the production of many viruses using the Vero cell line can be found in the literature. However, the vast majority of these processes is relying on the microcarrier technology. While this system is established for the large-scale manufacturing of viral vaccine, it is still quite complex and labor intensive. Moreover, scale-up remains difficult and is limited by the surface area given by the carriers. To overcome these and other drawbacks and to establish more efficient manufacturing processes, it is a priority to further develop the Vero cell platform by applying novel bioprocess technologies. Especially in times like the current COVID-19 pandemic, advanced and scalable platform technologies could provide more efficient and cost-effective solutions to meet the global vaccine demand. Herein, we review the prevailing literature on Vero cell bioprocess development for the production of viral vectors and vaccines with the aim to assess the recent advances in bioprocess development. We critically underline the need for further research activities and describe bottlenecks to improve the Vero cell platform by taking advantage of recent developments in the cell culture engineering field.

Citing Articles

Intensification of Vero cell adherence to microcarrier particles during cultivation in a wave bioreactor.

Mazhed Z, Vasilenko V, Siniugina A, Kaa K, Motov A, Pokidova K Front Bioeng Biotechnol. 2025; 13:1542060.

PMID: 40028290 PMC: 11868258. DOI: 10.3389/fbioe.2025.1542060.

Serum-Free Suspension Culture of the C6/36 Cell Line for Chimeric Orthoflavivirus Vaccine Production.

Dawurung J, Harrison J, Modhiran N, Hall R, Hobson-Peters J, de Malmanche H Viruses. 2025; 17(2).

PMID: 40007005 PMC: 11860912. DOI: 10.3390/v17020250.

Enhanced replication of a hepatitis A virus vaccine strain via adaptation in Vero cells.

Seo S, Choi J, Kim M, Yang E, Choi S, Seo D Clin Exp Vaccine Res. 2025; 14(1):10-22.

PMID: 39927228 PMC: 11799578. DOI: 10.7774/cevr.2025.14.e10.

Antiviral Activity of the Marine Haptophyta .

Montuori E, Ambrosino A, Sala G, Ragozzino C, Franci G, Zannella C Mar Drugs. 2025; 23(1).

PMID: 39852513 PMC: 11766726. DOI: 10.3390/md23010012.

Construction of a Vero cell line expression human KREMEN1 for the development of CVA6 vaccines.

Zhang D, Zou Y, Wu J, Xu L, Ke Z, Wu Y Virol J. 2025; 22(1):12.

PMID: 39825444 PMC: 11742515. DOI: 10.1186/s12985-024-02618-1.

References

Ma H, Ma Y, Ma W, Williams D, Galvin T, Khan A . Chemical induction of endogenous retrovirus particles from the vero cell line of African green monkeys. J Virol. 2011; 85(13):6579-88. PMC: 3126517. DOI: 10.1128/JVI.00147-11. View

Rourou S, Ben Ayed Y, Trabelsi K, Majoul S, Kallel H . An animal component free medium that promotes the growth of various animal cell lines for the production of viral vaccines. Vaccine. 2014; 32(24):2767-9. DOI: 10.1016/j.vaccine.2014.02.040. View

Leinonen H, Lipponen E, Valkama A, Hynynen H, Oruetxebarria I, Turkki V . Preclinical Proof-of-Concept, Analytical Development, and Commercial Scale Production of Lentiviral Vector in Adherent Cells. Mol Ther Methods Clin Dev. 2019; 15:63-71. PMC: 6804948. DOI: 10.1016/j.omtm.2019.08.006. View

Rhim J, Schell K, Creasy B, Case W . Biological characteristics and viral susceptibility of an African green monkey kidney cell line (Vero). Proc Soc Exp Biol Med. 1969; 132(2):670-8. DOI: 10.3181/00379727-132-34285. View

Mise-Omata S, Obata Y, Iwase S, Mise N, Doi T . Transient strong reduction of PTEN expression by specific RNAi induces loss of adhesion of the cells. Biochem Biophys Res Commun. 2005; 328(4):1034-42. DOI: 10.1016/j.bbrc.2005.01.066. View

Racine T, Kobinger G, Arts E . Development of an HIV vaccine using a vesicular stomatitis virus vector expressing designer HIV-1 envelope glycoproteins to enhance humoral responses. AIDS Res Ther. 2017; 14(1):55. PMC: 5594459. DOI: 10.1186/s12981-017-0179-2. View

Abbate T, Dewasme L, Wouwer A . Variable selection and parameter estimation of viral amplification in vero cell cultures dedicated to the production of a dengue vaccine. Biotechnol Prog. 2018; 35(1):e2687. DOI: 10.1002/btpr.2687. View

Jaluria P, Betenbaugh M, Konstantopoulos K, Frank B, Shiloach J . Application of microarrays to identify and characterize genes involved in attachment dependence in HeLa cells. Metab Eng. 2007; 9(3):241-51. PMC: 2001267. DOI: 10.1016/j.ymben.2006.12.001. View

White L, Ades E . Growth of Vero E-6 cells on microcarriers in a cell bioreactor. J Clin Microbiol. 1990; 28(2):283-6. PMC: 269591. DOI: 10.1128/jcm.28.2.283-286.1990. View

10.

Schmieder V, Bydlinski N, Strasser R, Baumann M, Kildegaard H, Jadhav V . Enhanced Genome Editing Tools For Multi-Gene Deletion Knock-Out Approaches Using Paired CRISPR sgRNAs in CHO Cells. Biotechnol J. 2017; 13(3):e1700211. DOI: 10.1002/biot.201700211. View

11.

Barrett P, Mundt W, Kistner O, Howard M . Vero cell platform in vaccine production: moving towards cell culture-based viral vaccines. Expert Rev Vaccines. 2009; 8(5):607-18. DOI: 10.1586/erv.09.19. View

12.

Liu C, Lian W, Butler M, Wu S . High immunogenic enterovirus 71 strain and its production using serum-free microcarrier Vero cell culture. Vaccine. 2006; 25(1):19-24. DOI: 10.1016/j.vaccine.2006.06.083. View

13.

Toriniwa H, Komiya T . Japanese encephalitis virus production in Vero cells with serum-free medium using a novel oscillating bioreactor. Biologicals. 2007; 35(4):221-6. DOI: 10.1016/j.biologicals.2007.02.002. View

14.

Chan J, Chan K, Choi G, To K, Tse H, Cai J . Differential cell line susceptibility to the emerging novel human betacoronavirus 2c EMC/2012: implications for disease pathogenesis and clinical manifestation. J Infect Dis. 2013; 207(11):1743-52. PMC: 7107374. DOI: 10.1093/infdis/jit123. View

15.

Lesch H, Heikkila K, Lipponen E, Valonen P, Muller A, Rasanen E . Process Development of Adenoviral Vector Production in Fixed Bed Bioreactor: From Bench to Commercial Scale. Hum Gene Ther. 2015; 26(8):560-71. DOI: 10.1089/hum.2015.081. View

16.

Sugawara K, Nishiyama K, Ishikawa Y, Abe M, Sonoda K, Komatsu K . Development of Vero cell-derived inactivated Japanese encephalitis vaccine. Biologicals. 2002; 30(4):303-14. DOI: 10.1006/biol.2002.0345. View

17.

Rourou S, van der Ark A, Majoul S, Trabelsi K, van der Velden T, Kallel H . A novel animal-component-free medium for rabies virus production in Vero cells grown on Cytodex 1 microcarriers in a stirred bioreactor. Appl Microbiol Biotechnol. 2009; 85(1):53-63. DOI: 10.1007/s00253-009-2064-y. View

18.

Silva A, Delgado I, Sousa M, Carrondo M, Alves P . Scalable culture systems using different cell lines for the production of Peste des Petits ruminants vaccine. Vaccine. 2008; 26(26):3305-11. DOI: 10.1016/j.vaccine.2008.03.077. View

19.

Grein T, Loewe D, Dieken H, Weidner T, Salzig D, Czermak P . Aeration and Shear Stress Are Critical Process Parameters for the Production of Oncolytic Measles Virus. Front Bioeng Biotechnol. 2019; 7:78. PMC: 6478815. DOI: 10.3389/fbioe.2019.00078. View

20.

Nikolay A, Castilho L, Reichl U, Genzel Y . Propagation of Brazilian Zika virus strains in static and suspension cultures using Vero and BHK cells. Vaccine. 2017; 36(22):3140-3145. DOI: 10.1016/j.vaccine.2017.03.018. View