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Title: Antigenic epidemiology of foot-and-mouth disease : understanding the limitations of in-vitro vaccine matching for Malaysian strains
Author: Binti Senawi, Jamaliah
ISNI:       0000 0004 8502 9987
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2019
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Foot-and mouth disease (FMD) is highly transmissible between all cloven-hoofed animals and is considered a livestock disease of great importance due to its impact upon productivity and the trade restrictions. The aetiological agent is an RNA virus classified into seven serotypes: A, O, C, Asia 1, SAT 1, SAT 2 and SAT 3. Despite considerable global research efforts, serological in-vitro tests, such as virus neutralisation test (VNT) and liquid phase blocking ELISA (LPBE), are still the only methods for vaccine selection. Although, these assays are relatively simple to perform, they are known to be highly variable and the accuracy of the resulting relationship coefficient (r1-values) is often questioned. The overall aim of the thesis was to identify the source of variability that impacts the relationship coefficient (r1-values) and understand the limitations of the invitro vaccine-matching tests. Therefore, three main factors, thought to contribute to this variability, were investigated: (i) cellular, (ii) serological, and (iii) virus. The experimental design focused on the A/ASIA/Sea-97 lineage; a contemporary virus frequently detected in Southeast Asia that exhibits high antigenic variability in in-vitro vaccine matching tests. The impact of cell replication cycle on virus and neutralisation titres, reflect on the variability of vaccine-matching tests. Thus, it is recommended that fully confluent cells are used to reduce the variability. Further, the source of the variability in the vaccine-matching tests is also attributed to the low of day-to-day repeatability of the serological tests and the inherent differences between individual post vaccinal sera. Consequently, variability in in-vitro vaccine matching assays can be reduced by pooling sera from different animals and performing the tests for field and vaccine viruses simultaneously. Although, measuring different spectrum of antibodies, results obtained using VNT are more inconsistent than those of LPBE. The importance of FMDV antigen integrity on variability of in-vitro vaccine matching tests was shown to be multifactorial; even in related strains, viral capsid dissociates at different temperatures and the level of dissociated capsid particles varies in different viruses. Interestingly, the A-May-97 vaccine virus was found to be more unstable than the field strains. Field evaluation of post vaccination immune response in Peninsular Malaysia indicated that the vaccine used is effective and able to confer protection against the contemporary field virus, despite poor vaccine-matching results. In conclusion, the current serological tests can be useful indicators for vaccine selection; there are simple and affordable but the r1 values need further attention as well as improvement, and, ideally, should be linked to protection.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: QR Microbiology