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Optimisation of a recombinant Hepatitis B vaccine through the cultivation and fermentation of Aspergillus Niger
Thesis (MScEng (Process Engineering))--University of Stellenbosch, 2005.
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| Format: | Thesis |
| Language: | English |
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Stellenbosch : University of Stellenbosch
2008
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| _version_ | 1867613923617800192 |
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| access_status_str | Open Access |
| author | James, Emmanuel Robin |
| author2 | Gorgens, Johann F. |
| author_browse | Gorgens, Johann F. James, Emmanuel Robin |
| author_facet | Gorgens, Johann F. James, Emmanuel Robin |
| author_sort | James, Emmanuel Robin |
| collection | Thesis |
| dc_rights_str_mv | University of Stellenbosch |
| description | Thesis (MScEng (Process Engineering))--University of Stellenbosch, 2005. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/1698 |
| institution | Stellenbosch University (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:43:51.865Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2008 |
| publishDateRange | 2008 |
| publishDateSort | 2008 |
| publisher | Stellenbosch : University of Stellenbosch |
| publisherStr | Stellenbosch : University of Stellenbosch |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/1698 Optimisation of a recombinant Hepatitis B vaccine through the cultivation and fermentation of Aspergillus Niger James, Emmanuel Robin Gorgens, Johann F. Van Zyl, Willem Heber University of Stellenbosch. Faculty of Engineering. Dept. of Process Engineering. Dissertations -- Process engineering Theses -- Process engineering Hepatitis B vaccine Aspergillus niger Biochemical engineering Hepatitis B Thesis (MScEng (Process Engineering))--University of Stellenbosch, 2005. The development of non-replicating vaccines is an emerging option for safe, effective vaccines, several of which contain virus-like particles (VLPs). Many recombinant expression systems have been evaluated as hosts for VLP production for the prevention of infectious diseases. The filamentous fungi Aspergillus niger has emerged as a potential alternative expression system for cost effective VLP vaccine production. Hepatitis B surface antigen (HBsAg) was used as a model VLP product to benchmark A. niger’s production capacity with those of Saccharomyces cerevisiae, Pichia pastoris and Hansenula polymorpha. Bioprocessing strategies were used to optimise VLP production by recombinant A. niger in batch culture. In particular, the effect of the parameters culture temperature, inoculum concentration, agitation intensity, dissolved oxygen (dO2) concentration and culture pH on biomass formation, morphology and VLP (HBsAg) production concentration was quantified. At an optimum agitation of 100 rpm and optimum dO2 concentration of 50 %, HBsAg production levels were increased 9-fold compared to yields obtained in shakeflask cultivation. Highest HBsAg production levels of 3.6 mg.ℓculture -1 and 350 μg.gDW -1 were recorded, at a biomass concentration of 10.5 gDW.ℓculture -1. These production levels compare favourable with those obtained by other production systems under similar conditions. HBsAg VLPs mostly accumulated intracellularly, although under optimum bioreactor conditions significant HBsAg accumulation in the cytoplasm and culture supernatant was also observed. The impact of these process parameters on VLP production and cell morphology was attributed to environmental stress conditions. Volumetric biomass and HBsAg production levels were maximised under conditions of lowest environmental stress, resulting in the most optimal small-pelleted morphology. These results indicate a substantial potential for further engineering of the A. niger production system for the high level of intracellular and extracellular VLP production. Masters 2008-07-15T12:02:58Z 2010-06-01T08:31:00Z 2008-07-15T12:02:58Z 2010-06-01T08:31:00Z 2005-12 Thesis http://hdl.handle.net/10019.1/1698 en University of Stellenbosch application/pdf Stellenbosch : University of Stellenbosch |
| spellingShingle | Dissertations -- Process engineering Theses -- Process engineering Hepatitis B vaccine Aspergillus niger Biochemical engineering Hepatitis B James, Emmanuel Robin Optimisation of a recombinant Hepatitis B vaccine through the cultivation and fermentation of Aspergillus Niger |
| title | Optimisation of a recombinant Hepatitis B vaccine through the cultivation and fermentation of Aspergillus Niger |
| title_full | Optimisation of a recombinant Hepatitis B vaccine through the cultivation and fermentation of Aspergillus Niger |
| title_fullStr | Optimisation of a recombinant Hepatitis B vaccine through the cultivation and fermentation of Aspergillus Niger |
| title_full_unstemmed | Optimisation of a recombinant Hepatitis B vaccine through the cultivation and fermentation of Aspergillus Niger |
| title_short | Optimisation of a recombinant Hepatitis B vaccine through the cultivation and fermentation of Aspergillus Niger |
| title_sort | optimisation of a recombinant hepatitis b vaccine through the cultivation and fermentation of aspergillus niger |
| topic | Dissertations -- Process engineering Theses -- Process engineering Hepatitis B vaccine Aspergillus niger Biochemical engineering Hepatitis B |
| url | http://hdl.handle.net/10019.1/1698 |
| work_keys_str_mv | AT jamesemmanuelrobin optimisationofarecombinanthepatitisbvaccinethroughthecultivationandfermentationofaspergillusniger |