Multistage production of Autographa californica nuclear polyhedrosis virus in insect cell cultures

Klöppinger, Martina; Fertig, Georg; Fraune, Elisabeth; Miltenburger, H.G.

doi:10.1007/bf00563787

Cited by 50 publications

(29 citation statements)

References 5 publications

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“…Glucose uptake was similar in the two cases, but lactate accumulated significantly in the bioreactor indicating inadequate oxygen supply. Kloppinger et al (1990) found that a dissolved oxygen concentration of 40% was necessary to optimize the production of wild-type virus in a bioreactor. In a bioreactor infection with Sf-9 cells at 6 × 10 5 cells/mL, found that the dissolved oxygen fell to zero and stayed there for 90 h without DO control.…”

Section: Discussionmentioning

confidence: 99%

Effect of elevated oxygen and glutamine levels on foreign protein production at high cell densities using the insect cell-baculovirus expression system

Taticek

Shuler

1997

Biotechnol. Bioeng.

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Section: Discussionmentioning

confidence: 99%

Effect of elevated oxygen and glutamine levels on foreign protein production at high cell densities using the insect cell-baculovirus expression system

Taticek

Shuler

1997

Biotechnol. Bioeng.

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“…More resent work indicates that the cultivation of mammalian cells generally can be undertaken satisfactorily from 5% to 100% of air saturation (Oh et al 1989). Insect cells have been reported to have a narrower operating range of 40-60% (Klopinger et al 1990), though there is also some work indicating that they are similar to mammalian cells (Kioukia et al 1996). The overall oxygen demand of the cells throughout the cultivation (including post-infection in the case of insect cells) must be met by the oxygen transfer rate and the demand increases as long as the number of viable cells is increasing.…”

Section: Mass Transfer Performance and Oxygen Demandmentioning

confidence: 99%

“…Optimum dO 2 levels for cultivation (Klopinger et al 1990) from 40% to 60% potentially give a reduced driving force for oxygen transfer. Both these aspects suggest that insect cells may require higher agitation and/or aeration intensity.…”

Section: Insect Culture Post-infectionmentioning

confidence: 99%

Reactor Engineering in Large Scale Animal Cell Culture

2006

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This article mainly addresses the issues associated with the engineering of large-scale free suspension culture in agitated bioreactors >10,000 L because they have become the system of choice industrially. It is particularly concerned with problems that become increasingly important as the scale increases. However, very few papers have been written that are actually based on such large-scale studies and the few that do rarely address any of the issues quantitatively. Hence, it is necessary very often to extrapolate from small-scale work and this review tries to pull the two types of study together. It is shown that 'shear sensitivity' due to agitation and bursting bubbles is no longer considered a major problem. Homogeneity becomes increasingly important with respect to pH and nutrients at the largest scale and sub-surface feeding is recommended despite 'cleaning in place' concerns. There are still major questions with cell retention/recycle systems at these scales, either because of fouling, of capacity or of potential and different 'shear sensitivity' questions. Fed-batch operation gives rise to cell densities that have led to the use of oxygen and enriched air to meet oxygen demands. This strategy, in turn, gives rise to a CO 2 evolution rate that impacts on pH control, pCO 2 and osmolality. These interactions are difficult to resolve but if higher sparge and agitation intensities could be used to achieve the necessary oxygen transfer, the problem would largely disappear. Thus, the perception of 'shear sensitivity' is still impacting on the development of animal cell culture at the commercial scale. Microcarrier culture is also briefly addressed. Finally, some recommendations for bioreactor configuration and operating strategy are given.

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“…The optimal pO 2 value for Sf-9 cell growth is, however, dependent upon the medium and bioreactor type used. In fact, in serum-containing medium, in a 1.5 dm 3 stirred tank with bubble-free aeration the specific growth rate at a pO 2 of 60 or 80% was lower than the one measured at 20 and 40% (Klöppinger et al, 1990). In 18 dm 3 stirred tanks with microsparging, pO 2 values of 10 and 110% lead to a reduction of 25% in the specific growth rate when compared to a pO 2 of 65% (Jain et al, 1991).…”

Section: Discussionmentioning

confidence: 64%

Optimization of the production of virus-like particles in insect cells

Cruz

Cunha

Peixoto

et al. 1998

Biotechnol. Bioeng.

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In this work the maximal operational hydrodynamic conditions (agitation and aeration rate) that cause no adverse effect in Sf‐9 cells growth in SF900II serum‐free medium were determined. Shear stresses higher than 1 N m−2 and aeration rates higher than 0.04 vvm affect cell growth and when these conditions increase to 1.5 N m−2 and 0.11 vvm, cell growth is completely inhibited with significant cell morphology changes and a strong decrease in viability. Although the pO2 did not show a significant effect upon cell growth in the range from 10 to 50%, cell infection and specific productivity were dramatically affected. The production was optimal at a pO2 of 25% with decreases higher than 50% being observed when the pO2 decreased to 10 or increased to 50%. The maximum product quality, i.e., the percentage of product in the form of high molecular weight particles, is not coincident with maximum product titer. Although the highest Pr55gag particle titer was obtained at 96 hours post infection (hpi) and at pO2 of 25%, the best product quality (defined by gel filtration chromatography and Western immunoblot) was obtained at 48 hpi, independently of the pO2 used. The effect of overcritical conditions upon productivity was also studied. As obtained for cell growth, cell infection is affected by shear stresses above 1 N m−2 and by aeration rates higher than 0.04 vvm, with decreases in Pr55gag particle titer higher than 70%, even when the overcritical values are still far from the limit at which cell death occurs. The results obtained and the optimization strategy used allowed the maximization of the oxygen supply without damaging the cells, with important consequences on the scale‐up of a production process involving this insect cell/baculovirus expression system. © 1998 John Wiley & Sons, Inc. Biotechnol Bioeng 60: 408–418, 1998.

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Multistage production of Autographa californica nuclear polyhedrosis virus in insect cell cultures

Cited by 50 publications

References 5 publications

Effect of elevated oxygen and glutamine levels on foreign protein production at high cell densities using the insect cell-baculovirus expression system

Effect of elevated oxygen and glutamine levels on foreign protein production at high cell densities using the insect cell-baculovirus expression system

Reactor Engineering in Large Scale Animal Cell Culture

Optimization of the production of virus-like particles in insect cells

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