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SAT2 foot-and-mouth disease virus (FMDV) structurally modified for increased thermostability

DOI: 10.1128/JVI.02312-16 DOI Help

Authors: Katherine A. Scott (ARC-Onderstepoort Veterinary Institute; University of Pretoria) , Abhay Kotecha (University of Oxford) , Julian Seago (Pirbright Institute) , Jingshan Ren (University of Oxford) , Elizabeth E. Fry (University of Oxford) , David I. Stuart (Diamond Light Source; University of Oxford) , Bryan Charleston (The Pirbright Institute) , Francois F. Maree (ARC-Onderstepoort Veterinary Institute; University of Pretoria)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Virology

State: Published (Approved)
Published: March 2017

Abstract: Foot-and-mouth disease virus (FMDV) is notoriously unstable, particularly the O and SAT serotypes. Consequently, vaccines derived from heat-labile SAT viruses have been linked to the induction of poor duration immunity and hence require more frequent vaccinations to ensure protection. In-silico calculations predicted residue substitutions that would increase interactions at the inter-pentameric interface supporting increased stability. We assessed the stability of the 18 recombinant mutant viruses for their growth kinetics; antigenicity; plaque morphology; genetic stability; temperature, ionic and pH stability using the thermofluor and inactivation assays, in order to evaluate potential SAT2 vaccine candidates with improved stability. The most stable mutation was the single mutant S2093Y for temperature and pH stability, whilst other promising single mutants were E3198A, L2094V,S2093H and the triple mutant F2062Y-H2087M-H3143V. Although the S2093Y mutant had the greatest stability it exhibited smaller plaques; a reduced growth rate; a change in a monoclonal antibody footprint, and poor genetic stability properties compared to the wild-type virus. However, these factors affecting production can be overcome. The addition of 1M NaCl salt was found to further increase the stability of the SAT2 panel of viruses. The S2093Y and S2093H mutants were selected for future use in stabilising SAT2 vaccines.

Diamond Keywords: Foot-and-Mouth Disease (FMD); Viruses

Subject Areas: Medicine, Biology and Bio-materials

Technical Areas:

Added On: 27/03/2017 16:18

Discipline Tags:

Vaccines Pathogens Infectious Diseases Structural biology Drug Discovery Life Sciences & Biotech Veterinary Medicine

Technical Tags: