Chimeric O1K foot-and-mouth disease virus with SAT2 outer capsid as an FMD vaccine candidate

DOI: 10.1038/s41598-018-31856-x

Authors: Abhay Kotecha (University of Oxford) , Eva Perez-Martin (The Pirbright Institute) , Yongjie Harvey (The Pirbright Institute) , Fuquan Zhang (The Pirbright Institute) , Serban L. Ilca (Wellcome Trust Centre for Human Genetics, University of Oxford) , Elizabeth E. Fry (Wellcome Trust Centre for Human Genetics, University of Oxford) , Ben Jackson (The Pirbright Institute) , Francois Maree (ARC-Onderstepoort Veterinary Institute) , Katherine Scott (ARC-Onderstepoort Veterinary Institute) , Corey W. Hecksel (Diamond Light Source) , Michiel M. Harmsen (Wageningen Bioveterinary Research, Division Virology) , Valérie Mioulet (The Pirbright Institute) , Britta Wood (The Pirbright Institute) , Nick Juleff (The Pirbright Institute) , David I. Stuart (Diamond Light Source) , Bryan Charleston (The Pirbright Institute) , Julian Seago (The Pirbright Institute)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Scientific Reports , VOL 8

State: Published (Approved)
Published: September 2018

Abstract: Foot-and-mouth disease virus (FMDV) is highly contagious and infects cloven-hoofed domestic livestock leading to foot-and-mouth disease (FMD). FMD outbreaks have severe economic impact due to production losses and associated control measures. FMDV is found as seven distinct serotypes, but there are numerous subtypes within each serotype, and effective vaccines must match the subtypes circulating in the field. In addition, the O and Southern African Territories (SAT) serotypes, are relatively more thermolabile and their viral capsids readily dissociate into non-immunogenic pentameric subunits, which can compromise the effectiveness of FMD vaccines. Here we report the construction of a chimeric clone between the SAT2 and O serotypes, designed to have SAT2 antigenicity. Characterisation of the chimeric virus showed growth kinetics equal to that of the wild type SAT2 virus with better thermostability, attributable to changes in the VP4 structural protein. Sequence and structural analyses confirmed that no changes from SAT2 were present elsewhere in the capsid as a consequence of the VP4 changes. Following exposure to an elevated temperature the thermostable SAT2-O1K chimera induced higher neutralizing-antibody titres in comparison to wild type SAT2 virus.

Journal Keywords: Biotechnology; Viral infection

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

Subject Areas: Biology and Bio-materials

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios I-Titan Krios I at Diamond

Added On: 24/09/2018 11:49

Documents:
s41598-018-31856-x.pdf

Discipline Tags:

Vaccines Pathogens Infectious Diseases Agriculture & Fisheries Drug Discovery Life Sciences & Biotech Veterinary Medicine

Technical Tags:

Microscopy Electron Microscopy (EM) Cryo Electron Microscopy (Cryo EM)