Tracking the antigenic evolution of foot-and-mouth disease virus

Reeve, R. et al. (2016) Tracking the antigenic evolution of foot-and-mouth disease virus. PLoS ONE, 11(7), e0159360. (doi: 10.1371/journal.pone.0159360) (PMID:27448206) (PMCID:PMC4957747)

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Quantifying and predicting the antigenic characteristics of a virus is something of a holy grail for infectious disease research because of its central importance to the emergence of new strains, the severity of outbreaks, and vaccine selection. However, these characteristics are defined by a complex interplay of viral and host factors so that phylogenetic measures of viral similarity are often poorly correlated to antigenic relationships. Here, we generate antigenic phylogenies that track the phenotypic evolution of two serotypes of foot-and-mouth disease virus by combining host serology and viral sequence data to identify sites that are critical to their antigenic evolution. For serotype SAT1, we validate our antigenic phylogeny against monoclonal antibody escape mutants, which match all of the predicted antigenic sites. For serotype O, we validate it against known sites where available, and otherwise directly evaluate the impact on antigenic phenotype of substitutions in predicted sites using reverse genetics and serology. We also highlight a critical and poorly understood problem for vaccine selection by revealing qualitative differences between assays that are often used interchangeably to determine antigenic match between field viruses and vaccine strains. Our approach provides a tool to identify naturally occurring antigenic substitutions, allowing us to track the genetic diversification and associated antigenic evolution of the virus. Despite the hugely important role vaccines have played in enhancing human and animal health, vaccinology remains a conspicuously empirical science. This study advances the field by providing guidance for tuning vaccine strains via site-directed mutagenesis through this high-resolution tracking of antigenic evolution of the virus between rare major shifts in phenotype.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Reeve, Professor Richard and Harvey, Dr William and Parida, Professor Satya
Authors: Reeve, R., Borley, D. W., Maree, F. F., Upadhyaya, S., Lukhwareni, A., Esterhuysen, J. J., Harvey, W. T., Blignaut, B., Fry, E. E., Parida, S., Paton, D. J., and Mahapatra, M.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN (Online):1932-6203
Published Online:22 July 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in PLoS ONE 11(7):e0159360
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
518811Towards the strategic control of foot-and-mouth disease in Africa: new techniques for a neglected problemSarah CleavelandBiotechnology and Biological Sciences Research Council (BBSRC)BB/H009302/1RI BIODIVERSITY ANIMAL HEALTH & COMPMED
507161Improving the quality of FMD (Foot-and-mouth disease) vaccines by understanding the correlation of vaccine-induced protection with humoral and cellular immune responsesRichard ReeveBiotechnology and Biological Sciences Research Council (BBSRC)BB/H009175/1RI BIODIVERSITY ANIMAL HEALTH & COMPMED