Downstream processing and chromatography based analytical methods for production of vaccines, gene therapy vectors, and bacteriophages

Kramberger, Petra; Urbas, Lidija; Štrancar, Aleš

doi:10.1080/21645515.2015.1009817

Cited by 74 publications

(65 citation statements)

References 65 publications

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“…At low ligand density the LP4 fraction contained a ratio of 4.59 VP/IVP, MP5 had 5.12, and HP6 4.00 VP/ IVP all are within accepted ranges for clinical use(Kramberger et al, 2015) and despite the different ligand densities presenting unique elution profiles with product eluting at different conductivities, the highest titre peaks (LP4, MP5, and HP6) showed a relatively consistent infective ratio. The ratio of viral particles to infective viral particles or units (VP/IVP) is often used as an indicator of product quality.…”

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confidence: 68%

“…Monoliths have been applied to Ad5 purification (Whitfield, Battom, Barut, Gilham, & Ball, 2009) as well as the separation of much larger enveloped virus species including Vaccinia viruses (350 nm; Vincent et al, 2017). The final infective coefficient of virus particle per infective virus particles (VP/IVP) was 13, a range documented as acceptable for potency by the Food and Drug Administration (Kramberger, Urbas, & Štrancar, 2015). Previous reports showed that the CIM™ QA-1 was preferable over the weak anion CIM™ DEAE-1.…”

Section: Introductionmentioning

confidence: 99%

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Adenovirus 5 recovery using nanofiber ion‐exchange adsorbents

Turnbull

Wright

Green

et al. 2019

Biotech & Bioengineering

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Viral vectors such as adenovirus have successful applications in vaccines and gene therapy but the manufacture of the high-quality virus remains a challenge. It is desirable to use the adsorption-based chromatographic separations that so effectively underpin the therapeutic protein manufacture. However fundamental differences in the size and stability of this class of product mean it is necessary to revisit the design of sorbent's morphology and surface chemistry. In this study, the behaviour of a cellulose nanofiber ion-exchange sorbent derivatised with quaternary amine ligands at defined densities is characterised to address this. This material was selected as it has a large accessible surface area for viral particles and rapid process times. Initially, the impact of surface chemistry on infective product recovery using low (440 µmol/g), medium (750 µmol/g), and high (1029 µmol/g) ligand densities is studied. At higher densities product stability is reduced, this effect increased with prolonged adsorption durations of 24 min with just~10% loss at low ligand density versus~50% at high. This could be mitigated by using a high flow rate to reduce the cycle time to~1 min. Next, the impact of ligand density on the separation's resolution was evaluated. Key to understanding virus quality is the virus particle: infectious virus particle ratio. It was found this parameter could be manipulated using ligand density and elution strategy. Together this provides a basis for viral vector separations that allows for their typically low titres and labile nature by using high liquid velocity to minimise both load and on-column times while separating key product and process-related impurities.

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mentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Adenovirus 5 recovery using nanofiber ion‐exchange adsorbents

Turnbull

Wright

Green

et al. 2019

Biotech & Bioengineering

View full text Add to dashboard Cite

show abstract

“…For the sake of brevity, a discussion of downstream processing was omitted. Please refer to the following articles for further downstream processing information: [56][57][58].…”

Section: Manufacturing and Engineering Dna Vaccinesmentioning

confidence: 99%

Engineering DNA vaccines against infectious diseases

et al. 2018

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Engineering vaccine-based therapeutics for infectious diseases is highly challenging, as trial formulations are often found to be nonspecific, ineffective, thermally or hydrolytically unstable, and/or toxic. Vaccines have greatly improved the therapeutic landscape for treating infectious diseases and have significantly reduced the threat by therapeutic and preventative approaches. Furthermore, the advent of recombinant technologies has greatly facilitated growth within the vaccine realm by mitigating risks such as virulence reversion despite making the production processes more cumbersome. In addition, seroconversion can also be enhanced by recombinant technology through kinetic and nonkinetic approaches, which are discussed herein. Recombinant technologies have greatly improved both amino acid-based vaccines and DNA-based vaccines. A plateau of interest has been reached between 2001 and 2010 for the scientific community with regard to DNA vaccine endeavors. The decrease in interest may likely be attributed to difficulties in improving immunogenic properties associated with DNA vaccines, although there has been research demonstrating improvement and optimization to this end. Despite improvement, to the extent of our knowledge, there are currently no regulatory body-approved DNA vaccines for human use (four vaccines approved for animal use). This article discusses engineering DNA vaccines against infectious diseases while discussing advantages and disadvantages of each, with an emphasis on applications of these DNA vaccines. STATEMENT OF SIGNIFICANCE: This review paper summarizes the state of the engineered/recombinant DNA vaccine field, with a scope entailing "Engineering DNA vaccines against infectious diseases". We endeavor to emphasize recent advances, recapitulating the current state of the field. In addition to discussing DNA therapeutics that have already been clinically translated, this review also examines current research developments, and the challenges thwarting further progression. Our review covers: recombinant DNA-based subunit vaccines; internalization and processing; enhancing immune protection via adjuvants; manufacturing and engineering DNA; the safety, stability and delivery of DNA vaccines or plasmids; controlling gene expression using plasmid engineering and gene circuits; overcoming immunogenic issues; and commercial successes. We hope that this review will inspire further research in DNA vaccine development.

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“…Associated with filtration procedures, (liquid) chromatography technologies are now widely used to reduce viral contamination of biological/biopharmaceutical products such as monoclonal antibodies (mAbs) [12] and blood products [3]. They have also become a major step in bioseparation schemes for the recovery/purification of viruses or virus-like particles, with a view to large-scale production of high-purity viral stocks needed for manufacture of safer vaccines and viral vectors for gene therapy [13,14]. In the search for improved tools against viral contamination and infections, chromatographic adsorbents based on PS -agarose (AG) and CEL, essentially, and dextran, to a lesser extent (Table 1) -have proven to be materials of choice for virus purification and virus removal.…”

Section: Introductionmentioning

confidence: 99%