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Improved stability of foot-and-mouth disease virus (FMDV) SAT2 capsid
Thesis (PhD)--University of Pretoria, 2016.
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| Format: | Thesis |
| Language: | English |
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University of Pretoria
2017
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| _version_ | 1867613635910565888 |
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| access_status_str | Open Access |
| author2 | Maree, Francois Frederick |
| author_browse | Maree, Francois Frederick |
| author_facet | Maree, Francois Frederick |
| collection | Thesis |
| dc_rights_str_mv | © 2016 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. |
| description | Thesis (PhD)--University of Pretoria, 2016. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/60130 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:39:17.410Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2017 |
| publishDateRange | 2017 |
| publishDateSort | 2017 |
| publisher | University of Pretoria |
| publisherStr | University of Pretoria |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/60130 Improved stability of foot-and-mouth disease virus (FMDV) SAT2 capsid Maree, Francois Frederick scottka@arc.agric.za Quan, Melvyn Scott, Katherine Anne UCTD Reverse genetics Virus Vaccine Foot-and-mouth disease Thermostability Thesis (PhD)--University of Pretoria, 2016. The thermostability of vaccines is of crucial importance in Africa, where the logistical process to get the vaccine from the manufacturer to the animal may take months, and in many remote regions transport and storage is in the absence of a cold-chain. Vaccines with improved stability and less reliance on a cold-chain are needed and could improve the longevity of immune responses elicited in vaccinated animals. In South Africa, cattle in the vaccination zone neighbouring the Kruger National Park have to be vaccinated thrice annually because of declining antibody responses at three months postvaccination. FMDV is known to be unstable, especially for O and SAT2 serotypes in mildly acidic pH conditions or at elevated temperatures, leading to dissociation of the capsid (146S particle) and loss of immunogenicity. The link between rapidly declining antibody responses and capsid stability have been reported by Doel and Baccarini, 1981. We hypothesized that more stable viruses, especially thermostability, will not only improve the protective immune response in animals but also require less frequent booster vaccinations. The residues at the capsid inter-pentamer interfaces, and their interactions, are important for the infectivity and stability of the virion and mutations adjacent to these interfaces have an effect on the conformational stability of FMDV. However, experimental studies on the relative importance of residues and molecular interactions in viral capsid assembly, disassembly, and/or stability are still very limited, especially for the SAT serotypes of FMDV. This study investigated the effects of potential residues at the pentameric interfaces that are responsible for increased thermostability and potentially improved stability candidates were tested in small (guinea pigs) and large (cattle) animal vaccination trials to understand the role of stabilised antigens on immune responses. The biological variation in biophysical stability in SAT2 viruses in the southern Africa region was investigated to determine if any naturally occurring viruses have greater capsid thermostability. Naturally occurring stable viruses could be used as prospective candidates in vaccine production and therefore potentially result in increased duration of immune responses. Our first aim was to investigate the role of different amino acid changes at the interface and their effect on capsid stability using models derived by Oxford University. These changes were introduced by mutating the SAT2 ZIM7/83 infectious genome-length clone (pSAT2) to derive mutated chimeric SAT2 viruses. We quantified the stabilizing effects of these mutations by using various stability assays. We established the novel thermofluor shift assay that is able to quantify the capsid stability of viruses. The growth kinetics, antigenicity, genetic stability, pH and salt sensitivity were investigated for each of the genetically engineered viruses (Chapters 2 and 3). The second aim was to further our understanding on the correlation between improved stability and immune responses by performing small animal (Chapter 2) and large animals trials in cattle (Chapter 4) and comparing stabilised and wild-type antigens. This study for the first time for SAT vaccines, determined differences in IgG1 and IgG2 profiles, interferon gamma (IFN-γ) responses and differences in total and neutralising antibodies of stabilised and wild-type antigens over a six month period in cattle (Chapter 4). Animals were intra-dermolingually challenged with live virus to determine levels of protection the antigens have afforded. In addition, a third aim will be to better understand the inherent thermostability variation of SAT2 viruses in the Southern African region (Chapter 5) by establishing a protocol for screening field isolates as potential vaccine strains and correlating their stability to amino acid residues at the interface of the 146S particles. Agricultural Research Council Veterinary Tropical Diseases PhD Unrestricted 2017-04-28T12:52:26Z 2017-04-28T12:52:26Z 2017 2016 Thesis Scott, KA 2016, Improved stability of foot-and-mouth disease virus (FMDV) SAT2 capsid, PhD Thesis, University of Pretoria, Pretoria, viewed yymmdd <http://hdl.handle.net/2263/60130> A2017 http://hdl.handle.net/2263/60130 en © 2016 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria |
| spellingShingle | UCTD Reverse genetics Virus Vaccine Foot-and-mouth disease Thermostability Improved stability of foot-and-mouth disease virus (FMDV) SAT2 capsid |
| title | Improved stability of foot-and-mouth disease virus (FMDV) SAT2 capsid |
| title_full | Improved stability of foot-and-mouth disease virus (FMDV) SAT2 capsid |
| title_fullStr | Improved stability of foot-and-mouth disease virus (FMDV) SAT2 capsid |
| title_full_unstemmed | Improved stability of foot-and-mouth disease virus (FMDV) SAT2 capsid |
| title_short | Improved stability of foot-and-mouth disease virus (FMDV) SAT2 capsid |
| title_sort | improved stability of foot and mouth disease virus fmdv sat2 capsid |
| topic | UCTD Reverse genetics Virus Vaccine Foot-and-mouth disease Thermostability |
| url | http://hdl.handle.net/2263/60130 |