Investigating the manufacturing technology for a novel live vaccine strain for Glässer’s disease

Thomas, R 2014, Investigating the manufacturing technology for a novel live vaccine strain for Glässer’s disease, Doctor of Philosophy (PhD), Applied Sciences, RMIT University.

Document type: Thesis
Collection: Theses

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Title Investigating the manufacturing technology for a novel live vaccine strain for Glässer’s disease
Author(s) Thomas, R
Year 2014
Abstract Glässer’s disease is a common bacterial disease among weaning pigs that causes large economic losses to the pig industries worldwide. The etiologic agent of Glässer’s disease is Haemophilus parasuis which is associated with lung infections, fibrinous polyserositis, arthritis and/or septicaemia in swine population resulting in significant levels of mortality and morbidity. Control measures such as antibiotics and autogenous vaccines lack adequate control over this organism Commercial vaccines are largely based on killed antigen and hence lack effectiveness due to the poor cross-reactivity between H. parasuis serovars. It is expected that live vaccines, due to their ability to replicate within the host, will evoke a stronger and more cross-protective immune response compared to humoral immunity induced by killed vaccines.

Development of commercial medium for the live attenuated vaccine is challenging as H. parasuis is a fastidious that is very difficult to grow in culture. The primary aim of the project was to develop and design a liquid based medium suitable for cultivating an attenuated vaccine candidate at industrial scale. In order to produce this vaccine to large scale production, the media components must comply with international regulatory standards. Once high yields of viable strain is produced, the organisms must be adequately preserved for stability during storage and transport of vaccine vials. Therefore the optimisation of a freeze dry based preservation program and preservatives was also examined.

The diagnosis of H. parasuis depends upon the ability to isolate and differentiate this organism from other organisms that may be present in a clinical sample. The fragile nature of H. parasuis makes this bacterium difficult to isolate and diagnose. Differential diagnosis is useful for the purpose of differentiating the vaccine strains from field H. parasuis species, especially post vaccination. This project aims to develop molecular methodology to differentiate and identify the vaccine strain from its own parent strain as well as closely related species for better diagnosis. Multilocus sequence typing based on house-keeping genes is s a highly discriminative genotyping method. It was also explored in this project to generate a specific profile for H. parasuis Australian isolates and to compare directly with global H. parasuis spp.
Degree Doctor of Philosophy (PhD)
Institution RMIT University
School, Department or Centre Applied Sciences
Subjects Veterinary Microbiology (excl. Virology)
Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies)
Veterinary Epidemiology
Keyword(s) Haemophilus parasuis
Glasser's disease
optimisation of media
multilocus sequence typing
optimisation of physical parameters
polymerase chain reaction
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Created: Wed, 05 Sep 2018, 11:39:40 EST by Keely Chapman
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