A Novel Oscillating Bioreactor BelloCell: Implications for Insect Cell Culture
and Recombinant Protein Production

Lu, Juin-Ming; Chung, Yao-Chi; Chan, Zun-Ren; Hu, Yu‐Chen

doi:10.1007/s10529-005-8450-3

Cited by 18 publications

(7 citation statements)

References 11 publications

(16 reference statements)

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“…An example is the multilayered hyper flasks from Corning ® with scaled-up volume (up to 10 times) on which cells can be grown ( ). Another example is the BelloCell ® from CESCO Bioengineering Inc. ( 44 ). The principle of the BelloCell is that of alternating nutrient and gaseous exchange.…”

Section: Antigen Productionmentioning

confidence: 99%

Oral Vaccination of Fish – Antigen Preparations, Uptake, and Immune Induction

2015

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The oral route offers the most attractive approach of immunization of fish for a number of reasons: the ease of administration of antigens, it is less stressful than parenteral delivery and in principle, it is applicable to small and large sized fish; it also provides a procedure for oral boosting during grow-out periods in cages or ponds. There are, however, not many commercial vaccines available at the moment due to lack of efficacy and challenges associated with production of large quantities of antigens. These are required to stimulate an effective immune response locally and systemically, and need to be protected against degradation before they reach the sites where immune induction occurs. The hostile stomach environment is believed to be particularly important with regard to degradation of antigens in certain species. There is also a poor understanding about the requirements for proper immune induction following oral administration on one side, and the potential for induction of tolerance on the other. To what extent primary immunization via the oral route will elicit both local and systemic responses is not understood in detail. Furthermore, to what extent parenteral delivery will protect mucosal/gut surfaces and vice-versa is also not fully understood. We review the work that has been done on the subject and discuss it in light of recent advances that include mass production of antigens, including the use of plant systems. Different encapsulation techniques that have been developed in the quest to protect antigens against digestive degradation, as well as to target them for appropriate immune induction are also highlighted.

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Section: Antigen Productionmentioning

confidence: 99%

Oral Vaccination of Fish – Antigen Preparations, Uptake, and Immune Induction

2015

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“…1A) has a top lid equipped with a 0.22-m pore size filter for ventilation and is prepacked with BioNOC II carriers (CESCO Bioengineering) for cell immobilization (Chen et al, 2005). The compressible lower chamber (i.e., the "bellow") can be alternately compressed and released by the BelloStage (CESCO Bioengineering), with a linear moving rate ranging between 0.5 and 2 mm/sec (Lu et al, 2005). The compression raises the medium to submerge the carriers, thus allowing for nutrient transfer.…”

Section: Bellocell Reactor Configuration and Operationmentioning

confidence: 99%

Combination of Baculovirus-Mediated Gene Delivery and Packed-Bed Reactor for Scalable Production of Adeno-Associated Virus

Huang

Chung

et al. 2007

Human Gene Therapy

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The production of recombinant adeno-associated virus (rAAV) commonly requires plasmid cotransfection, which hinders its mass production. Herein we describe the development of a novel process for rAAV production by combining the advantages of baculovirus-mediated gene delivery and BelloCell bioreactor (a novel packed-bed reactor for animal cell culture; CESCO Bioengineering, Hsinchu, Taiwan). We constructed three baculoviral vectors: Bac-LacZ carries the lacZ gene flanked by AAV inverted terminal repeats, Bac-RC harbors AAV rep and cap genes, and Bac-Helper carries helper genes derived from adenovirus. Cotransduction of HEK-293 cells with these three baculoviruses resulted in successful production of rAAV, and the protein and rAAV yield did not decrease with Bac-RC passage for up to four passages. By adjusting the dose ratio of Bac-LacZ to Bac-RC, adding sodium butyrate, and transferring the production process to the BelloCell-500-AP (500 ml), which allowed for high-density culture and effective baculovirus-mediated transduction of HEK-293 cells, the maximal specific rAAV yield reached approximately 3.8 x 10(4) vector genome (VG) or 247 infectious viral particles (IVP) per cell, which corresponded to approximately 1 x 10(14) VG or 8.5 x 10(11) IVP per reactor run. The yield was comparable or superior to those obtained with other production systems. Baculoviral transduction is simple and cost-effective and the BelloCell-500-AP offers high-density culture of HEK-293 cells. Altogether, the combination of baculoviral transduction and BelloCell reactor culture provides a novel and economically viable approach for rAAV production.

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“…The BelloCell bioreactors have been successfully used to cultivate mammalian cells for the production of HDV-like particles [15], Japanese encephalitis virus [16], and insect cells for baculovirus [17]. In these studies, the bioreactors have consistently shown various beneficial characteristics: (1) Improved efficiency because they are pre-sterile and ready-to-use, (2) low shear stress because they move the liquid gently without the generation of gas bubbles, (3) large surface area to achieve a high-density growth of cells, and (4) the ability to collect whole cells or cell components [15, 18, 19]. At present, the use of these single-use bioreactors for influenza vaccine production has not been reported.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of novel disposable bioreactors on pandemic influenza virus production

et al. 2019

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Since 1997, the highly pathogenic influenza H5N1 virus has spread from Hong Kong. According to the WHO bulletin report, the H5N1 virus is a zoonotic disease threat that has infected more than 850 humans, causing over 450 deaths. In addition, an outbreak of another new and highly pathogenic influenza virus (H7N9) occurred in 2013 in China. These highly pathogenic influenza viruses could potentially cause a worldwide pandemic. it is crucial to develop a rapid production platform to meet this surge demand against any possible influenza pandemic. A potential solution for this problem is the use of cell-based bioreactors for rapid vaccine production. These novel bioreactors, used for cell-based vaccine production, possess various advantages. For example, they enable a short production time, allow for the handling highly pathogenic influenza in closed environments, and can be easily scaled up. In this study, two novel disposable cell-based bioreactors, BelloCell and TideCell, were used to produce H5N1 clade II and H7N9 candidate vaccine viruses (CVVs). Madin-Darby canine kidney (MDCK) cells were used for the production of these influenza CVVs. A novel bench-scale bioreactor named BelloCell bioreactor was used in the study. All culturing conditions were tested and scaled to 10 L industrial-scale bioreactor known as TideCell002. The performances of between BelloCell and TideCell were similar in cell growth, the average MDCK cell doubling time was slightly decreased to 25 hours. The systems yielded approximately 39.2 and 18.0 μg/ml of HA protein with the 10-liter TideCell002 from the H5N1 clade II and H7N9 CVVs, respectively. The results of this study not only highlight the overall effectiveness of these bioreactors but also illustrate the potential of maintaining the same outcome when scaled up to industrial production, which has many implications for faster vaccine production. Although additional studies are required for process optimization, the results of this study are promising and show that oscillating bioreactors may be a suitable platform for pandemic influenza virus production.

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A Novel Oscillating Bioreactor BelloCell: Implications for Insect Cell Culture and Recombinant Protein Production

Cited by 18 publications

References 11 publications

Oral Vaccination of Fish – Antigen Preparations, Uptake, and Immune Induction

Oral Vaccination of Fish – Antigen Preparations, Uptake, and Immune Induction

Combination of Baculovirus-Mediated Gene Delivery and Packed-Bed Reactor for Scalable Production of Adeno-Associated Virus

Evaluation of novel disposable bioreactors on pandemic influenza virus production

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