dc.contributor.author | Kotecha, Abhay | |
dc.contributor.author | Seago, Julian | |
dc.contributor.author | Scott, Katherine Anne | |
dc.contributor.author | Burman, Alison | |
dc.contributor.author | Loureiro, Silvia | |
dc.contributor.author | Ren, Jingshan | |
dc.contributor.author | Porta, Claudine | |
dc.contributor.author | Ginn, Helen M. | |
dc.contributor.author | Jackson, Terry | |
dc.contributor.author | Perez-Martin, Eva | |
dc.contributor.author | Siebert, C. Alistair | |
dc.contributor.author | Paul, Guntram | |
dc.contributor.author | Huiskonen, Juha T. | |
dc.contributor.author | Jones, Ian M. | |
dc.contributor.author | Esnouf, Robert M. | |
dc.contributor.author | Fry, Elizabeth E. | |
dc.contributor.author | Maree, Francois Frederick | |
dc.contributor.author | Charleston, Bryan | |
dc.contributor.author | Stuart, David I. | |
dc.date.accessioned | 2016-02-18T10:37:44Z | |
dc.date.issued | 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 | http://www.nature.com/nsmb | 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.identifier.uri | http://hdl.handle.net/2263/51454 | |
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 |