SCIENTIFIC PUBLICATIONS

Our purification technology can achieve >98% recovery for different AAV serotypes and recombinant variants using a single standardized setup:

Marichal-Gallardo P, et al. Single-use capture purification of adeno-associated viral gene transfer vectors by membrane-based steric exclusion chromatography.

Human Gene Therapy 2021;32(17–18):959–974.

DOI: https://doi.org/10.1089/hum.2019.284

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MVA virus is successfully captured and purified using our SXC technology in semi-continuous mode:

Gränicher G, et al. A high cell density perfusion process for Modified Vaccinia Ankara production: process integration with inline DNA digestion and cost analysis.

Biotechnology & Bioengineering 2021;118:4720–4734.

DOI: https://doi.org/10.1002/bit.27937

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Virus particles purified and concentrated with our membrane-based SXC technology lead to complete abrogation of SARS-CoV-2 replication in vitro:

Rand U, et al. Antiviral activity of influenza A virus defective interfering particles against SARS-CoV-2 replication in vitro through stimulation of innate immunity.

Cells 2021;10(7)

DOI: https://doi.org/10.3390/cells10071756

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Single-use SXC yields up to 300 purified influenza vaccine doses per Litre of cell culture::

Bissinger T, et al. Towards integrated production of an influenza A vaccine candidate with MDCK suspension cells.

Biotechnology & Bioengineering 2021;118:3996–4013.

DOI: https://doi.org/10.1002/bit.27876

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Our SXC technology allowed significant removal of impurities and is a promising technique for future integration of upstream and downstream operations of yellow fever virus-like particles:

Alvin R, et al. Process intensification for the production of yellow fever virus-like particles (VLPs) as potential recombinant vaccine antigen.

Biotechnology & Bioengineering 2021;118:3581–3592.

DOI: https://doi.org/10.1002/bit.27864

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Product recovery of 92% and highest biological activity in animal tests for defective interfering particles (DIPs) of influenza virus purified with our membrane-based SXC technology:

Hein M, et al. Cell culture-based production and in vivo characterization of purely clonal defective interfering influenza virus particles.

BMC Biology 2021;19:91

DOI: https://doi.org/10.1186/s12915-021-01020-5

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An influenza particle with antiviral activity purified with membrane-based SXC was the most affective in stopping influenza infection in mice:

Hein M, et al. OP7, a novel influenza A virus defective interfering particle: production, purification, and animal experiments demonstrating antiviral potential.

Applied Microbiology and Biotechnology 2021;105:129–146

DOI: https://doi.org/10.1007/s00253-020-11029-5

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Virtually full recovery for inactivated hepatitis C virus using membrane-based SXC:

Lothert K, et al. Development of a downstream process for the production of an inactivated whole hepatitis C virus vaccine.

Scientific Reports 2020;1016261.

DOI: https://doi.org/10.1038/s41598-020-72328-5

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Membrane-based SXC is used as a capture step for the purification of Orf virus with 84% product recovery:

Lothert K, et al. Selection of chromatographic methods for the purification of cell culture-derived Orf virus for its application as a vaccine or viral vector.

Journal of Biotechnology 2020;323:62–72.

DOI: https://doi.org/10.1016/j.jbiotec.2020.07.023

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Average baculovirus recovery of 91% without decreasing the transduction efficacy using membrane-based SXC:

Lothert K, et al. SMembrane-based steric exclusion chromatography for the purification of a T recombinant baculovirus and its application for cell therapy..

Journal of Virological Methods 2020;275:113756.

DOI: https://doi.org/10.1016/j.jviromet.2019.113756

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Engineering of SXC for the capture & purification of different viral particles used in vaccine and gene therapy applications:

Marichal-Gallardo P, Chromatographic purification of biological macromolecules by their capture on hydrophilic surfaces with the aid of non-ionic polymers.

Dissertation, Otto-von-Guericke University Magdeburg; Nov 2020.

DOI: http://dx.doi.org/10.25673/33035

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Engineering of cell culture techniques for the continuous production of MVA and influenza A virus:

Tapia F, Continuous upstream processing for cell culture-derived virus production.

Dissertation, Otto-von-Guericke University Magdeburg; Nov 2020.

DOI: http://dx.doi.org/10.25673/33531

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Our tubular bioreactor could continually produce influenza A virus for over 3 weeks and is the only production system that avoids the accumulation of defective interfering particles:

Tapia F, et al. Continuous influenza virus production in a tubular bioreactor system provides stable titers and avoids the “von Magnus effect.”

PLoS ONE 2019;14:e0224317–1.

DOI: https://doi.org/10.1371/journal.pone.0224317

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Our purification technology achieves 20–40% more recovery (>98%) for influenza A virus compared to existing purification methods by using a disposable device:

Marichal-Gallardo P, et al. Steric exclusion chromatography for purification of cell culture-derived influenza A virus using regenerated cellulose membranes and polyethylene glycol.

Journal of Chromatography A 2017;1483:110–119.

DOI: https://doi.org/10.1016/j.chroma.2016.12.076

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We show stable continuous production of MVA virus for over 3 weeks using a cascade of two stirred tanks:

Tapia F, et al. Efficient and stable production of Modified Vaccinia Ankara virus in two-stage semi-continuous and in continuous stirred tank cultivation systems.

PLoS ONE 2017;12:e0182553–17.

DOI: https://doi.org/10.1371/journal.pone.0182553

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Review article with the latest trends in continuous cultivations of suspension cells for the production of virus particles:

Tapia F, et al. Bioreactors for high cell density and continuous multi-stage cultivations: options for process intensification in cell culture-based viral vaccine production.

Applied Microbiology and Biotechnology 2016;100:2121–2132.

DOI: https://doi.org/10.1007/s00253-015-7267-9

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CONFERENCE TALKS & POSTERS

Conference Talks

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Our purification technology is the only single-use chromatography method which purifies a wide variety of viruses (influenza virus, yellow fever virus, Vaccinia virus, AAV) with typical yields above 95% at high flow rate using a one-size-fits-all setup:

Marichal-Gallardo P, et al.

A single-use chromatographic purification platform for viral gene transfer vectors & viral vaccines.

Advancing Manufacture of Cell and Gene Therapies VI

Coronado, CA, USA. January 2019

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Our purification technology yielded more than 100 000 doses of yellow fever vaccine in less than 3 hours without product losses and with impurity levels below the regulatory requirements for human vaccines:

Marichal-Gallardo P, et al.

Purifying viruses with a sheet of paper: Single-use steric exclusion chromatography as a capture platform for vaccine candidates.

Vaccine Technology VII

Mont Tremblant, Canada. June 2018

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Our production technology has 20x smaller volumes is the only bioreactor system that enables stable virus production over weeks and without accumulation of mutant viruses.

Tapia, F, et al.

Multi-stage bioreactor concepts for continuous virus vaccine production.

Continuous Biomanufacturing: Achievements and Challenges for Commercial Implementation

Oxford, UK, 2018

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PATENTS

WO2017190790A1, Tapia F, et al. Plug flow tubular bioreactor, system containing the same and method for production of virus. (Pending)

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WO2017076553A1, Wolff MW, et al. Method for the separation of virus compositions including depletion and purification thereof. (Pending)

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