Award details

Immunity to FMDV following combined DNA and inactivated virus antigen

Reference	BBS/E/I/00001316
Principal Investigator / Supervisor	Dr Paul Barnett
Co-Investigators / Co-Supervisors
Institution	The Pirbright Institute
Department	The Pirbright Institute Department
Funding type	Research
Value (£)	1,039,993
Status	Completed
Type	Institute Project
Start date	25/06/2007
End date	30/04/2012
Duration	59 months

Abstract

EU recognises vaccination as a principle means for FMD control, despite its inefficiencies including lack of a strong cellular response. DNA vaccines, in contrast, elicit a repertoire of effective immune responses as the encoded antigen is endogenously synthesised and processed, mimicking natural infection and targetting DC's and thus is presented via the MHC class I and class II pathways to generate durable humoral and cellular responses. Innate immunity is also triggered, partly through unmethylated CpG motifs. Other practical advantages include non-infectiousness, ease of manipulation, inexpense and thermostability, providing potential for emergency and endemic use, with scope to incorporate marker genes and cover "difficult" isolates. Cattle are the principle target of the susceptible domestic species and this programme will utilise FMD DNA vaccination to augment bovine immune responses and study their importance to both protection and persistence. Successive dosage with FMD and GMCSF DNA plasmids,will be compared with a prime-protein boost regime along with simultaneous DNA and protein immunisation to mimic emergency use. Humoral, cellular and innate parameters will confirm the optimal regime. T cell proliferation and IFNgamma ELIspot assays will estimate the memory T cells primed by DNA regimes and Th1 responses and the degree of recall antigen responding cells, and the phenotype of the cells will define the induced lymphocyte subset(s). Cytotoxic assays will establish whether a polarized Th1 or Th2 response is promoted. The ability of dendritic cells to present antigens to lymphocytes will be analysed to understand the mechanism by which DNA vaccine works in vivo. Protection studies, will be monitored for at least 28 days post challenge, to assess persistence, the various immune parameters and the efficacy of the DNA vaccine regime. Key non-structural protein antibody responses will be examined to differentiate vaccinates supporting viral persistence.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Animal Health, Immunology, Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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