DSC_5122_edited.png

PUBLICATIONS

ContiVir is based on a strong scientific foundation from many years of research at the Bioprocess Engineering Group of the Max Planck Institute for Dynamics of Complex Technical Systems in Magdeburg, Germany.

Our technologies are grounded on both patents and scientific publications in respected peer-reviewed journals.

We also list selected talks and posters in several respected scientific conferences around the world.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

 

CONFERENCE TALKS & POSTERS

Conference Talks

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

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

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

 
 

PATENTS

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

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