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Reeve R.,University of Glasgow | Blignaut B.,Onderstepoort Veterinary Institute | Blignaut B.,University of Pretoria | Esterhuysen J.J.,Onderstepoort Veterinary Institute | And 13 more authors.
PLoS Computational Biology | Year: 2010

Identifying when past exposure to an infectious disease will protect against newly emerging strains is central to understanding the spread and the severity of epidemics, but the prediction of viral cross-protection remains an important unsolved problem. For foot-and-mouth disease virus (FMDV) research in particular, improved methods for predicting this cross-protection are critical for predicting the severity of outbreaks within endemic settings where multiple serotypes and subtypes commonly co-circulate, as well as for deciding whether appropriate vaccine(s) exist and how much they could mitigate the effects of any outbreak. To identify antigenic relationships and their predictors, we used linear mixed effects models to account for variation in pairwise cross-neutralization titres using only viral sequences and structural data. We identified those substitutions in surface-exposed structural proteins that are correlates of loss of cross-reactivity. These allowed prediction of both the best vaccine match for any single virus and the breadth of coverage of new vaccine candidates from their capsid sequences as effectively as or better than serology. Sub-sequences chosen by the modelbuilding process all contained sites that are known epitopes on other serotypes. Furthermore, for the SAT1 serotype, for which epitopes have never previously been identified, we provide strong evidence - by controlling for phylogenetic structure - for the presence of three epitopes across a panel of viruses and quantify the relative significance of some individual residues in determining cross-neutralization. Identifying and quantifying the importance of sites that predict viral strain cross-reactivity not just for single viruses but across entire serotypes can help in the design of vaccines with better targeting and broader coverage. These techniques can be generalized to any infectious agents where cross-reactivity assays have been carried out. As the parameterization uses pre-existing datasets, this approach quickly and cheaply increases both our understanding of antigenic relationships and our power to control disease.

Seiradake E.,The Henry Wellcome Building for Genomic Medicine | Zhao Y.,The Henry Wellcome Building for Genomic Medicine | Lu W.,The Henry Wellcome Building for Genomic Medicine | Radu Aricescu A.,The Henry Wellcome Building for Genomic Medicine | Yvonne Jones E.,The Henry Wellcome Building for Genomic Medicine
Methods in Molecular Biology | Year: 2015

Mammalian protein expression systems are becoming increasingly popular for the production of eukaryotic secreted and cell surface proteins. Here we describe methods to produce recombinant proteins in adherent or suspension human embryonic kidney cell cultures, using transient transfection or stable cell lines. The protocols are easy to scale up and cost-effi cient, making them suitable for protein crystallization projects and other applications that require high protein yields. © Springer Science+Business Media New York 2015.

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