Specific ion effects on the particle size distributions of cell culture–derived influenza A virus particles within the Hofmeister series

Heyse, Anja; Wolff, Michael W.; Reichl, Udo

doi:10.1002/elsc.201600153

Cited by 12 publications

(14 citation statements)

References 45 publications

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“…The DCS measurements were carried out according to Pieler et al [12]. Briefly, a CPS DC24000 UHR disc centrifuge (CPS Instruments Inc., LA, USA) was used at 24 000 RPM with a 4-16% (w/v) sucrose gradient in the respective buffer.…”

Section: Virus Particle Size Distribution Measurement By Differentialmentioning

confidence: 99%

“…A/PR ADH VP contain larger N-glycan structures, which makes them more hydrophilic than A/PR SUS VP with smaller N-glycan structures. It has to be taken into account, however, that both systems have a very low critical stabilization concentration (CSC) and a high number of stabilizing ions [12], which are characteristics of a highly hydrophilic particle system [29]. Interestingly, however, the hydrophobic A/PR SUS particles seem to have a lower tendency toward aggregation in the screened buffers ( Fig.…”

Section: Viral Hemagglutinin N-glycan Fingerprintsmentioning

confidence: 99%

“…Life Sci. In a previous study [12] we investigated ion-specific effects on the particle size distributions and aggregation of influenza A (A/Puerto Rico/8/34 H1N1, A/PR) VP produced in adherent and suspension Madin Darby canine kidney (MDCK) cells. It has already been shown that the N-glycosylation of the influenza A virus surface protein hemagglutinin (HA) depends strongly on the host cell line [8][9][10][11], which might change the physicochemical properties of the whole VP.…”

Section: Introductionmentioning

confidence: 99%

“…First, the particle size distributions (PSD) of the VP were measured by differential centrifugal sedimentation (DCS) in a buffer known to induce aggregation, i.e., 20 mM NaCl 10 mM Tris-HCl pH 7.4, and a buffer not affecting the aggregation status, i.e., 60 mM NaCl 10 mM Tris-HCl pH 7.4 [12]. As an application, we investigate both of the A/PR samples produced in animal cell cultures.…”

Section: Introductionmentioning

confidence: 99%

“…It has already been shown that the N-glycosylation of the influenza A virus surface protein hemagglutinin (HA) depends strongly on the host cell line [8][9][10][11], which might change the physicochemical properties of the whole VP. In a previous study [12] we investigated ion-specific effects on the particle size distributions and aggregation of influenza A (A/Puerto Rico/8/34 H1N1, A/PR) VP produced in adherent and suspension Madin Darby canine kidney (MDCK) cells. However, the experimental setup used did not allow for a more comprehensive investigation of the underlying causes for the differences in aggregation behavior.…”

Section: Introductionmentioning

confidence: 99%

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Influence of the production system on the surface properties of influenza A virus particles

Hämmerling

Hennig

Serve

et al. 2017

Engineering in Life Sciences

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In this study, influenza A/Puerto Rico/8/34 H1N1 virus particles (VP) produced in adherent and suspension Madin Darby canine kidney cells were investigated with a broad analytical toolbox to obtain more information on the VP's surface properties potentially affecting their aggregation behavior. First, differences in aggregation behavior were revealed by VP size distributions obtained via differential centrifugal sedimentation and confirmed by dynamic light scattering. The VP produced in adherent cells showed increased levels of aggregation in a 20 mM NaCl 10 mM Tris‐HCl pH 7.4 low‐salt buffer. This included the formation of multimers (dimers up to pentamers), whereas VP produced in suspension cells displayed no tendency toward aggregate formation. To investigate the cause of these differences in aggregation behavior, the VP samples were compared based on their zeta potential, their surface hydrophobicity, their lipid composition, and the N‐glycosylation of their major VP surface protein hemagglutinin. The zeta potential and the hydrophobicity of the VP produced in the adherent cells was significantly decreased compared to the VP produced in the suspension cells. The lipid composition of both VP systems was approximately identical. The hemagglutinin of the VP produced in adherent cells included more of the larger N‐glycans, whereas the VP produced in suspension cells included more of the smaller N‐glycans. These results indicate that differences in the glycosylation of viral surface proteins should be monitored to characterize VP hydrophobicity and aggregation behavior, and to avoid aggregate formation and product losses in virus purification processes for vaccines and gene therapy.

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Section: Virus Particle Size Distribution Measurement By Differentialmentioning

confidence: 99%

Section: Viral Hemagglutinin N-glycan Fingerprintsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Influence of the production system on the surface properties of influenza A virus particles

Hämmerling

Hennig

Serve

et al. 2017

Engineering in Life Sciences

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Towards integrated production of an influenza A vaccine candidate with MDCK suspension cells

Bissinger

Marichal-Gallardo

et al. 2021

Biotech & Bioengineering

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Seasonal influenza epidemics occur both in northern and southern hemispheres every year. Despite the differences in influenza virus surface antigens and virulence of seasonal subtypes, manufacturers are well‐adapted to respond to this periodical vaccine demand. Due to decades of influenza virus research, the development of new influenza vaccines is relatively straight forward. In similarity with the ongoing coronavirus disease 2019 pandemic, vaccine manufacturing is a major bottleneck for a rapid supply of the billions of doses required worldwide. In particular, egg‐based vaccine production would be difficult to schedule and shortages of other egg‐based vaccines with high demands also have to be anticipated. Cell culture‐based production systems enable the manufacturing of large amounts of vaccines within a short time frame and expand significantly our options to respond to pandemics and emerging viral diseases. In this study, we present an integrated process for the production of inactivated influenza A virus vaccines based on a Madin–Darby Canine Kidney (MDCK) suspension cell line cultivated in a chemically defined medium. Very high titers of 3.6 log10(HAU/100 µl) were achieved using fast‐growing MDCK cells at concentrations up to 9.5 × 106 cells/ml infected with influenza A/PR/8/34 H1N1 virus in 1 L stirred tank bioreactors. A combination of membrane‐based steric‐exclusion chromatography followed by pseudo‐affinity chromatography with a sulfated cellulose membrane adsorber enabled full recovery for the virus capture step and up to 80% recovery for the virus polishing step. Purified virus particles showed a homogenous size distribution with a mean diameter of 80 nm. Based on a monovalent dose of 15 µg hemagglutinin (single‐radial immunodiffusion assay), the level of total protein and host cell DNA was 58 µg and 10 ng, respectively. Furthermore, all process steps can be fully scaled up to industrial quantities for commercial manufacturing of either seasonal or pandemic influenza virus vaccines. Fast production of up to 300 vaccine doses per liter within 4–5 days makes this process competitive not only to other cell‐based processes but to egg‐based processes as well.

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Functionalized Smart Nanomaterials for Point-of-Care Testing

Lala,

Kotal,

Jana

2023

Smart Nanomaterials Technology

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Specific ion effects on the particle size distributions of cell culture–derived influenza A virus particles within the Hofmeister series

Cited by 12 publications

References 45 publications

Influence of the production system on the surface properties of influenza A virus particles

Influence of the production system on the surface properties of influenza A virus particles

Towards integrated production of an influenza A vaccine candidate with MDCK suspension cells

Functionalized Smart Nanomaterials for Point-of-Care Testing

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