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

Abhay Kotecha,Yongjie Harvey,David I Stuart,Eva Perez-Martin,Valérie Mioulet,Michiel M Harmsen,Britta Wood,Francois Maree,Julian Seago,Fuquan Zhang,Corey W Hecksel,Elizabeth E Fry,Katherine Scott,Serban L Ilca,Ben Jackson,Nick Juleff,Bryan Charleston

doi:10.1038/s41598-018-31856-x

Abhay Kotecha, Yongjie Harvey + Show 15 more

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https://doi.org/10.1038/s41598-018-31856-x

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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.

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Foot-and-mouth disease virus (FMDV) is highly contagious and infects cloven-hoofed domestic livestock leading to foot-and-mouth disease (FMD)
To determine if the SAT2 structural proteins can be effectively processed by O serotype non-structural proteins (NSPs), we used a similar cloning strategy to generate a SAT2/O1Kaufbeuren (O1K) chimeric clone encoding the outer capsid proteins and the non-structural 2A product of SAT2 ZIM/7/83, with NSPs and VP4 from O1K13 (Fig. 1)
RNA transcribed from the SAT2/O1K clone and electroporated into BHK-21 cells gave rise to infectious FMDV

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Foot-and-mouth disease virus (FMDV) is highly contagious and infects cloven-hoofed domestic livestock leading to foot-and-mouth disease (FMD). 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. 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. IRES-mediated translation of the FMDV genome yields a single polyprotein that is processed proteolytically to generate intermediate precursors and mature proteins. During translation an intra-ribosomal self-processing event occurs at the C terminus of 2A, separating the region containing the capsid proteins (P1) and non-structural 2A from the rest of the polyprotein. Correspondence and requests for materials should be addressed to J.S.

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