Sequence-based prediction for vaccine strain selection and identification of antigenic variability in foot-and-mouth disease virus

Reeve, R. et al. (2010) Sequence-based prediction for vaccine strain selection and identification of antigenic variability in foot-and-mouth disease virus. PLoS Computational Biology, 6(12), e1001027. (doi:10.1371/journal.pcbi.1001027)

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Abstract

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 model-building 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Haydon, Professor Daniel and Reeve, Dr Richard and Matthews, Professor Louise
Authors: Reeve, R., Blignaut, B., Esterhuysen, J.J., Opperman, P., Matthews, L., Fry, E.E., de Beer, T.A.P., Theron, J., Rieder, E., Vosloo, W., O'Neill, H.G., Haydon, D.T., and Maree, F.F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
Journal Name:PLoS Computational Biology
Publisher:Public Library of Science
ISSN:1553-734X
ISSN (Online):1553-7358
Published Online:09 December 2010
Copyright Holders:Copyright © 2010 The Authors
First Published:First published in PLoS Computational Biology 6(12):e1001027
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
437231Predicting immunological cross-reactivity - from genotype to antigenic phenotypeDaniel HaydonBiotechnology and Biological Sciences Research Council (BBSRC)BB/E010326/1Institute of Biodiversity Animal Health and Comparative Medicine