Structure-based energetics of protein interfaces guides foot-and-mouth disease virus vaccine design

Show simple item record Kotecha, Abhay Seago, Julian Scott, Katherine Anne Burman, Alison Loureiro, Silvia Ren, Jingshan Porta, Claudine Ginn, Helen M. Jackson, Terry Perez-Martin, Eva Siebert, C. Alistair Paul, Guntram Huiskonen, Juha T. Jones, Ian M. Esnouf, Robert M. Fry, Elizabeth E. Maree, Francois Frederick Charleston, Bryan Stuart, David I. 2016-02-18T10:37:44Z 2015-10
dc.description.abstract Virus capsids are primed for disassembly, yet capsid integrity is key to generating a protective immune response. Foot-and-mouth disease virus (FMDV) capsids comprise identical pentameric protein subunits held together by tenuous noncovalent interactions and are often unstable. Chemically inactivated or recombinant empty capsids, which could form the basis of future vaccines, are even less stable than live virus. Here we devised a computational method to assess the relative stability of protein-protein interfaces and used it to design improved candidate vaccines for two poorly stable, but globally important, serotypes of FMDV: O and SAT2. We used a restrained molecular dynamics strategy to rank mutations predicted to strengthen the pentamer interfaces and applied the results to produce stabilized capsids. Structural analyses and stability assays confirmed the predictions, and vaccinated animals generated improved neutralizing-antibody responses to stabilized particles compared to parental viruses and wild-type capsids. en_ZA
dc.description.embargo 2016-04-30
dc.description.librarian hb2015 en_ZA
dc.description.sponsorship Wellcome Trust (WT) for a Translation Award to fund this work (grant no. 089755). Biotechnology and Biological Sciences Research Council Institute Strategic Programme on Livestock Viral Diseases at The Pirbright Institute. The Oxford Particle Imaging Centre electron microscopy facility was founded by a WT Joint Infrastructure Fund award (060208/Z/00/Z) and is supported by a WT equipment grant (093305/Z/10/Z). The WT, UK Medical Research Council (MRC) and Biotechnology and Biology Research Council (grant no. G100099). en_ZA
dc.description.uri en_ZA
dc.identifier.citation Kotecha, K, Seago, J, Scott, KA, Burman, A, Loureiro, S, Ren, J, Porta, C, Ginn, HM, Jackson, T, Perez-Martin, E, Siebert, CA, Paul, G, Huiskonen, JT, Jones, IM, Esnouf, RM, Fry, EE, Maree, FF, Charleston, B & Stuart, D 2015, 'Structure-based energetics of protein interfaces guides foot-and-mouth disease virus vaccine design', Nature Structural and Molecular Biology, vol. 22, no. 10, pp. 1-10. en_ZA
dc.identifier.issn 1545-9993 (print)
dc.identifier.issn 1545-9985 (online)
dc.identifier.other 10.1038/nsmb.3096
dc.language.iso en en_ZA
dc.publisher Nature Publishing Group en_ZA
dc.rights Nature Publishing Group en_ZA
dc.subject Foot-and-mouth disease virus (FMDV) en_ZA
dc.subject Protein interfaces guides en_ZA
dc.subject Structural analyses en_ZA
dc.subject Stability en_ZA
dc.title Structure-based energetics of protein interfaces guides foot-and-mouth disease virus vaccine design en_ZA
dc.type Postprint Article en_ZA

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