Antibody Production by the Gram-Positive Bacterium Bacillus megaterium

Jordan, Eva; Al-Halabi, Laila; Schirrmann, Thomas; Hust, Michael

doi:10.1007/978-1-59745-554-1_27

Cited by 5 publications

(2 citation statements)

References 17 publications

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“…The Gram-positive bacteria Bacillus brevis (76, 77), Bacillus subtilis (78, 79), and Bacillus megaterium (80–85) have already been successfully used for the production of different antibody fragments. In addition, B. megaterium does not produce alkaline proteases and provides high stability of plasmid vectors during growth allowing stable transgene expression during long term cultivation in bioreactors (86).…”

Section: Antibody Production In Prokaryotic Hostsmentioning

confidence: 99%

Expression of Recombinant Antibodies

Frenzel¹,

Hust²,

Schirrmann³

2013

Front. Immunol.

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281

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Recombinant antibodies are highly specific detection probes in research, diagnostics, and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transgenic plants and animals. Currently, almost all therapeutic antibodies are still produced in mammalian cell lines in order to reduce the risk of immunogenicity due to altered, non-human glycosylation patterns. However, recent developments of glycosylation-engineered yeast, insect cell lines, and transgenic plants are promising to obtain antibodies with “human-like” post-translational modifications. Furthermore, smaller antibody fragments including bispecific antibodies without any glycosylation are successfully produced in bacteria and have advanced to clinical testing. The first therapeutic antibody products from a non-mammalian source can be expected in coming next years. In this review, we focus on current antibody production systems including their usability for different applications.

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Section: Antibody Production In Prokaryotic Hostsmentioning

confidence: 99%

Expression of Recombinant Antibodies

Frenzel¹,

Hust²,

Schirrmann³

2013

Front. Immunol.

Self Cite

281

220

View full text Add to dashboard Cite

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“…Recently, the Gram-positive bacterium B. megaterium was shown to efficiently secrete antibody fragments into the growth medium (Jordan et al, 2009). Amongst others, the lysozyme specific single chain Fv (scFv) fragment D1.3, an antibody fragment widely used to evaluate appropriate production methods, was successfully expressed and secreted using B. megaterium.…”

Section: Introductionmentioning

confidence: 99%

Optimization of antibody fragment production in Bacillus megaterium: The role of metal ions on protein secretion

David

Westphal

Bunk

et al. 2010

Journal of Biotechnology

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Influence of the hydromechanical stress and temperature on growth and antibody fragment production with Bacillus megaterium

Lüders

David

Steinwand

et al. 2011

Appl Microbiol Biotechnol

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Bacillus megaterium was used for production of the lysozyme-specific recombinant scFv D1.3 antibody fragment. Key process parameters like the temperature and the hydromechanical stress play a very important role for significant product formation during process development or scale-up. In this study, the influence of these two variables on growth and recombinant antibody fragment production in a 2-L lab-scale bioreactor system was investigated using a central composite design. Especially a significant influence of the hydromechanical stress on antibody fragment production was detected in batch cultivations. While volumetric power inputs of about 0.5 kW/m(3) (agitation rates around 500 min(-1)) are usually employed in batch cultivations, in this work maximal product concentration was found at a volumetric power input of about 0.06 kW/m(3) (agitation rate around 250 min(-1)) and at a high cultivation temperature of 41 °C. The influence of the two process variables at single-cell level was estimated using flow cytometry too. The characterization was done by estimating the membrane potential giving a hint on bioprocess productivity and secretion capability: the best production was obtained through big cells with low specific membrane potential, which grew at low volumetric power inputs and high cultivation temperatures.

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Antibody Production by the Gram-Positive Bacterium Bacillus megaterium

Cited by 5 publications

References 17 publications

Expression of Recombinant Antibodies

Expression of Recombinant Antibodies

Optimization of antibody fragment production in Bacillus megaterium: The role of metal ions on protein secretion

Influence of the hydromechanical stress and temperature on growth and antibody fragment production with Bacillus megaterium

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