Rapid production of a plasmid DNA encoding a malaria vaccine candidate via amino-functionalized poly(GMA-co-EDMA) monolith

Danquah, Michael K., Liu, Shan, Ho, Jenny, Forde, Gareth M., Wang, Lina, & Coppel, Ross L. (2008) Rapid production of a plasmid DNA encoding a malaria vaccine candidate via amino-functionalized poly(GMA-co-EDMA) monolith. AIChE Journal, 54(11), pp. 2990-2998.

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Abstract

Malaria is a global health problem; an effective vaccine is urgently needed. Due to the relative poverty and lack of infrastructure in malaria endemic areas, DNA-based vaccines that are stable at ambient temperatures and easy to formulate have great potential. While attention has been focused mainly on antigen selection, vector design and efficacy assessment, the development of a rapid and commercially viable process to manufacture DNA is generally overlooked. We report here a continuous purification technique employing an optimized stationary adsorbent to allow high-vaccine recovery, low-processing time, and, hence, high-productivity. A 40.0 mL monolithic stationary phase was synthesized and functionalized with amino groups from 2-Chloro-N,N- diethylethylamine hydrochloride for anion-exchange isolation of a plasmid DNA (pDNA) that encodes a malaria vaccine candidate, VR1020-PyMSP4/5. Physical characterization of the monolithic polymer showed a macroporous material with a modal pore diameter of 750 nm. The final vaccine product isolated after 3 min elution was homogeneous supercoiled plasmid with gDNA, RNA and protein levels in keeping with clinical regulatory standards. Toxicological studies of the pVR1020-PyMSP4/5 showed a minimum endotoxin level of 0.28 EU/m.g pDNA. This cost-effective technique is cGMP compatible and highly scalable for the production of DNA-based vaccines in commercial quantities, when such vaccines prove to be effective against malaria. © 2008 American Institute of Chemical Engineers.

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ID Code: 81551
Item Type: Journal Article
Refereed: Yes
Keywords: Liquid chromatography, Malaria vaccine, Methacrylate monolith, Plasmid DNA, ABS resins, Adsorption, Amination, Amines, Chromatographic analysis, Cost effectiveness, DNA, Genes, Nucleic acids, Organic acids, Process engineering, Purification, RNA, Ambient temperatures, Amino groups, Functionalized, Global healths, Infra structures, Macroporous materials, Malaria vaccines, Monolithic polymers, Physical characterizations, Plasmid dna (pdna), Plasmid dnas, Pore diameters, Processing times, Protein levels, Purification techniques, Regulatory standards, Stationary phase, Supercoiled, Vaccines
DOI: 10.1002/aic.11595
ISSN: 0001-1541
Divisions: Current > Schools > School of Chemistry, Physics & Mechanical Engineering
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Copyright Owner: Copyright 2008 American Institute of Chemical Engineers (AIChE)
Deposited On: 05 Feb 2015 22:58
Last Modified: 11 Feb 2015 04:21

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