Virus Production Under Suspension Conditions

Merten, Otto‐Wilhelm; Bakker, Wilfried A.M.; Vorlop, Jürgen; Reiter, Manfred; Visnovsky, Gabriel; Jäger, Volker; Merabishvili, Maia; Reichl, U.

doi:10.1002/9783527683321.ch14

Cited by 6 publications

(33 citation statements)

References 140 publications

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“…EB66 cells can be maintained in a serum-free medium named EX-CELL EBx-GRO-I that is animal-component-free (Olivier et al 2010). Hence, an efficient cell-based system has been provided and it can be applied as a safe, cheap and fast method for vaccine production (Merten et al 2014). The optimum cell culture to maintain chicken stem cells involved the use of defined medium and dynamic culture in feeder and serum-free conditions is shown in Figure 2 (Olivier et al 2010;Mehtali et al 2015).…”

Section: Suspension Culture Of Chicken Stem Cells For Largescale Prodmentioning

confidence: 99%

The evolution of chicken stem cell culture methods

Farzaneh

Attari

Mozdziak

et al. 2017

British Poultry Science

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1. The avian embryo is an excellent model for studying embryology and the production of pharmaceutical proteins in transgenic chickens. Furthermore, chicken stem cells have the potential for proliferation and differentiation and emerged as an attractive tool for various cell-based technologies. 2. The objective of these studies is the derivation and culture of these stem cells is the production of transgenic birds for recombinant biomaterials and vaccine manufacture, drug and cytotoxicity testing, as well as to gain insight into basic science, including cell tracking. 3. Despite similarities among the established chicken stem cell lines, fundamental differences have been reported between their culture conditions and applications. Recent conventional protocols used for expansion and culture of chicken stem cells mostly depend on feeder cells, serum-containing media and static culture. 4. Utilising chicken stem cells for generation of cell-based transgenic birds and a variety of vaccines requires large-scale cell production. However, scaling up the conventional adherent chicken stem cells is challenging and labour intensive. Development of a suspension cell culture process for chicken embryonic stem cells (cESCs), chicken primordial germ cells (PGCs) and chicken induced pluripotent stem cells (ciPSCs) will be an important advance for increasing the growth kinetics of these cells. 6. This review describes various approaches and suggestions to achieve optimal cell growth for defined chicken stem cells cultures and use in future manufacturing applications.

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Section: Suspension Culture Of Chicken Stem Cells For Largescale Prodmentioning

confidence: 99%

The evolution of chicken stem cell culture methods

Farzaneh

Attari

Mozdziak

et al. 2017

British Poultry Science

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“…First of all, diploid cell lines (or diploid cell strains) have been developed, which can actually be considered as primary cultures because they are created by passage of primary cultures. ,,, Later, continuous cell lines were developed to overcome the disadvantages of diploid cell lines, such as limited passage number, sensitive structure, and dependence on complex nutrient medium components. Continuous cell lines are defined as cells that are stable, can divide continuously, and can be cultured indefinitely in vitro under appropriate conditions. ,, However, at first, the fact that continuous cell lines were “immortal” led to thoughts that their use in production would be unsafe. ,, It took a long time for them to be used as cellular expression platforms in vaccine production, both because the techniques that would prove that their use was safe were insufficient at that time and because of the lack of studies on virus production on this subject. ,,,, It has been shown that continuous cell lines can be used in vaccine production after developing technology and determining the necessary rules to eliminate potential risks and obtaining all approvals. ,, …”

Section: Use Of Cell Lines In Vaccine Productionmentioning

confidence: 99%

“…In cell culture-based viral vaccine production, after determining the type of vaccine and production technology to be produced, the virus, viral antigen(s), or viral vector to be used as vaccine material must first be produced. Therefore, the expression platform that will produce them, that is, the cells, needs to be proliferated. ,,,, Although these productions can be carried out with static cell culture systems on a small scale, bioreactors are used due to the superior advantages they provide, especially in industrial productions where production takes place in large volumes. ,, Bioreactors are particularly suitable systems for scale-up, and thanks to their high controllability and automation features, they stand out in ensuring the necessary safety regulations and GMP conditions in vaccine production (Figure ). In the production of viral vaccines, production is carried out in large-scale bioreactors of different types and configurations, depending on the production feature of the chosen expression system.…”

Section: Selection Of the Expression Platformmentioning

confidence: 99%

“…The reason for this is that the available cellular substrates that will synthesize the desired component as a vaccine material in sufficient quantities and in the correct structure to have the appropriate immunogenicity have very different properties. If the vaccine component in the targeted production does not match the features of the selected platform, then successful production cannot be achieved. ,, Especially considering the type of vaccine desired to be produced, cellular substrates with appropriate properties that can be infected with the relevant virus and produce the virus or can correctly synthesize the viral antigen(s) to be used as vaccine material with genetic engineering must be selected. ,, Additionally, there is a direct approach for the expression platforms used to produce human vaccines should be of human origin. In this sense, some studies show that the vaccine material produced using human cell substrates expresses the virus in higher amounts and in more accurate forms in terms of viral specificity, since it is synthesized in the original virus-host relationship, and therefore provides more effective immunization. ,,, Along with these, after the selection of the appropriate cell line, the sublines derived from this cell line should also be evaluated.…”

Section: Selection Of the Expression Platformmentioning

confidence: 99%

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Animal Cell Lines as Expression Platforms in Viral Vaccine Production: A Post Covid-19 Perspective

Demirden,

Kimiz-Gebologlu,

Oncel

2024

ACS Omega

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Vaccines are considered the most effective tools for preventing diseases. In this sense, with the Covid-19 pandemic, the effects of which continue all over the world, humanity has once again remembered the importance of the vaccine. Also, with the various epidemic outbreaks that occurred previously, the development processes of effective vaccines against these viral pathogens have accelerated. By these efforts, many different new vaccine platforms have been approved for commercial use and have been introduced to the commercial landscape. In addition, innovations have been made in the production processes carried out with conventionally produced vaccine types to create a rapid response to prevent potential epidemics or pandemics. In this situation, various cell lines are being positioned at the center of the production processes of these new generation viral vaccines as expression platforms. Therefore, since the main goal is to produce a fast, safe, and effective vaccine to prevent the disease, in addition to existing expression systems, different cell lines that have not been used in vaccine production until now have been included in commercial production for the first time. In this review, first current viral vaccine types in clinical use today are described. Then, the reason for using cell lines, which are the expression platforms used in the production of these viral vaccines, and the general production processes of cell culture-based viral vaccines are mentioned. Also, selection parameters for animal cell lines as expression platforms in vaccine production are explained by considering bioprocess efficiency and current regulations. Finally, all different cell lines used in cell culture-based viral vaccine production and their properties are summarized, with an emphasis on the current and future status of cell cultures in industrial viral vaccine production.

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“…The only other surface-adherent cell line which had been scaled-up for large-scale production of a viral vaccine is the MDCK. Several different clones of MDCK (anchoragedependent and suspension-adapted clones) have been developed as cell substrate for influenza virus vaccine with a maximum production scale of 2500 l (microcarrierbased process) and of 10 000 l (suspension cell-based process) [53,54].…”

Section: (Iii) Subcultivation Of Anchorage-dependent Cells At Large Smentioning

confidence: 99%

Advances in cell culture: anchorage dependence

Merten

2015

Phil. Trans. R. Soc. B

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128

103

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Anchorage-dependent cells are of great interest for various biotechnological applications. (i) They represent a formidable production means of viruses for vaccination purposes at very large scales (in 1000-6000 l reactors) using microcarriers, and in the last decade many more novel viral vaccines have been developed using this production technology. (ii) With the advent of stem cells and their use/potential use in clinics for cell therapy and regenerative medicine purposes, the development of novel culture devices and technologies for adherent cells has accelerated greatly with a view to the large-scale expansion of these cells. Presently, the really scalable systems-microcarrier/ microcarrier-clump cultures using stirred-tank reactors-for the expansion of stem cells are still in their infancy. Only laboratory scale reactors of maximally 2.5 l working volume have been evaluated because thorough knowledge and basic understanding of critical issues with respect to cell expansion while retaining pluripotency and differentiation potential, and the impact of the culture environment on stem cell fate, etc., are still lacking and require further studies. This article gives an overview on critical issues common to all cell culture systems for adherent cells as well as specifics for different types of stem cells in view of small-and large-scale cell expansion and production processes.

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Virus Production Under Suspension Conditions

Cited by 6 publications

References 140 publications

The evolution of chicken stem cell culture methods

The evolution of chicken stem cell culture methods

Animal Cell Lines as Expression Platforms in Viral Vaccine Production: A Post Covid-19 Perspective

Advances in cell culture: anchorage dependence

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