Foot-and-mouth disease (FMD) is a highly contagious and economically
important disease that affects even-toed hoofed mammals. The FMD virus
(FMDV) is the causative agent of FMD, of which there are seven clinically
indistinguishable serotypes. Three serotypes, namely, South African
Territories (SAT)1, SAT2 and SAT3 are endemic to southern Africa and are
the most antigenically diverse among the FMDV serotypes. A negative
consequence of this antigenic variation is that infection or vaccination with
one virus may not provide immune protection from other strains or it may only
confer partial protection. The identification of B-cell epitopes is therefore key
to rationally designing cross-reactive vaccines that recognize the
immunologically distinct serotypes present within the population.
Computational epitope prediction methods that exploit the inherent physicochemical properties of epitopes in their algorithms have been
proposed as a cost and time-effective alternative to the classical experimental
methods. The aim of this project is to employ in silico epitope prediction
programmes to predict B-cell epitopes on the capsids of the SAT serotypes.
Sequence data for 18 immunologically distinct SAT1, SAT2 and SAT3 strains from across southern Africa were collated. Since, only one SAT1 virus has
had its structure elucidated by X-ray crystallography (PDB ID: 2WZR),
homology models of the 18 virus capsids were built computationally using
Modeller v9.12. They were then subjected to energy minimizations using the
AMBER force field. The quality of the models was evaluated and validated
stereochemically and energetically using the PROMOTIF and ANOLEA
servers respectively. The homology models were subsequently used as input
to two different epitope prediction servers, namely Discotope1.0 and Ellipro.
Only those epitopes predicted by both programmes were defined as epitopes.
Both previously characterised and novel epitopes were predicted on the SAT
strains. Some of the novel epitopes are located on the same loops as
experimentally derived epitopes, while others are located on a putative novel antigenic site, which is located close to the five-fold axis of symmetry. A
consensus set of 11 epitopes that are common on at least 15 out of 18 SAT
strains was collated. In future work, the epitopes predicted in this study will be
experimentally validated using mutagenesis studies. Those found to be true
epitopes may be used in the rational design of broadly reactive SAT vaccines / Life and Consumer Sciences / M. Sc. (Life Sciences)
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:unisa/oai:uir.unisa.ac.za:10500/21942 |
| Date | 24 January 2017 |
| Creators | Mukonyora, Michelle |
| Contributors | Rees, D. J. G., Maree, F. F. |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Dissertation |
| Format | 1 online resource (203 leaves) : color illustrations |
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