Hughson, MD; (2014) Micro-scale vaccine bioprocessing of a Japanese Encephalitis Virus vaccine. Doctoral thesis , UCL (University College London).

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Abstract

Japanese Encephalitis (JE) is the most common form of viral encephalitis in the world, caused by the Japanese Encephalitis virus (JEV), it is responsible for around 10,000 deaths a year whilst many more are left with long term neurological sequelae and disability. This work sought to use small-scale development techniques alongside high-throughput methodologies to explore and develop selected processing techniques. Formaldehyde inactivation of JEV was characterised and optimised through the use of Design of Experiments screening techniques where temperature, time and formaldehyde concentration were found to be key factors in antigen loss. Glycine and to a lesser extent sorbitol were found to have positive effects as stabilisers during inactivation at different stages of the process. Four anion exchange resins were screened at micro-scale, with the help of an ELISA method evaluated for high-throughput screening, for their potential to replace sucrose gradient purification as the principle purification step of the process. Although Q Sepharose FF was eventually chosen for scale-up studies, the transition of method and recovery rates from batch bind micro-plate studies to 1 mL column scale proved difficult. Yet it was observed that pre-treatment of feed with formaldehyde and glycine could increase JEV antigen recovery rates in flow-through mode chromatography, thought to be due to enhanced stability of the virus particles.

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