Simon P. Graham1,2
1The Pirbright Institute, Ash Road, Pirbright, GU24 ONF, UK
2School of Veterinary Medicine, University of Surrey, Guildford, GU2 7AL, UK
Abstracts:
CD8 T cells are crucial to the control of many viruses through cytolysis and cytokine secretion. With a view to informing vaccine development, we have been investigating the role of T cells in immunity to two major viral diseases of pigs; classical swine fever (CSF) and porcine reproductive and respiratory syndrome (PRRS).
Live attenuated CSFV vaccines provide rapid protection but their utility is limited by a lack of DIVA. To assess cellular mechanisms that may contribute to rapid protection, we explored the kinetics and specificity of T cells responses from vaccinated pigs challenged after one, three or five days with two diverse CSF virus (CSFV) isolates. T cell IFN-γ responses showed a close association with the protection observed. Polyfunctional CD8 T cells with effector/effector memory-like phenotypes were the dominant responding population. Antigenic regions/epitopes were highly conserved amongst CSFV strains and in some instance across pestivirus species, which may explain why a new chimeric pestiviral DIVA vaccine provides a comparably rapid onset of immunity.
The rapid evolution of the PRRS virus (PRRSV) poses a major challenge since available vaccines show variable efficacy against divergent strains. Since immunity to PRRSV is not dependent on neutralising antibodies, we hypothesised that conserved CD8 T cell antigens represent novel vaccine candidates. A PRRSV proteome-wide peptide library was screened to determine the specificity of T cell responses from cohorts of pigs immunised with divergent strains. Two immunodominant conserved antigens were identified and the responding T cell populations characterised. To assess their vaccine potential, these antigens were delivered using adjuvanted chitosan particles. Immunisation primed CD4 T cell responses that were associated with limited protection. Analysis of the lungs during the resolution of challenge infection showed high levels of specific CD8 T cells; suggesting that vaccine priming of this population is required for effective protection.