title: Characterisation of vaccine-induced, broadly cross-reactive IFN-γ secreting T cell responses that correlate with rapid protection against classical swine fever virus.
abstract: Live attenuated C-strain classical swine fever viruses (CSFV) provide a rapid onset of protection, but the lack of a serological test that can differentiate vaccinated from infected animals limits their application in CSF outbreaks. Since immunity may precede antibody responses, we examined the kinetics and specificity of peripheral blood T cell responses from pigs vaccinated with a C-strain vaccine and challenged after five days with a genotypically divergent CSFV isolate. Vaccinated animals displayed virus-specific IFN-γ responses from day 3 post-challenge, whereas, unvaccinated challenge control animals failed to mount a detectable response. Both CD4(+) and cytotoxic CD8(+) T cells were identified as the cellular source of IFN-γ. IFN-γ responses showed extensive cross-reactivity when T cells were stimulated with CSFV isolates spanning the major genotypes. To determine the specificity of these responses, T cells were stimulated with recombinant CSFV proteins and a proteome-wide peptide library from a related virus, BVDV. Major cross-reactive peptides were mapped on the E2 and NS3 proteins. Finally, IFN-γ was shown to exert potent antiviral effects on CSFV in vitro. These data support the involvement of broadly cross-reactive T cell IFN-γ responses in the rapid protection conferred by the C-strain vaccine and this information should aid the development of the next generation of CSFV vaccines.
authors.affiliation: Virology Department, Animal Health and Veterinary Laboratories Agency, Addlestone, United Kingdom. Simon.Graham@ahvla.defra.gsi.gov.uk
authors.forename: Simon P
authors.initials: SP
authors.lastname: Graham
authors.forename: Felicity J
authors.initials: FJ
authors.lastname: Haines
authors.forename: Helen L
authors.initials: HL
authors.lastname: Johns
authors.forename: Olubukola
authors.initials: O
authors.lastname: Sosan
authors.forename: S Anna
authors.initials: SA
authors.lastname: La Rocca
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lamp
authors.forename: Till
authors.initials: T
authors.lastname: Rümenapf
authors.forename: Helen E
authors.initials: HE
authors.lastname: Everett
authors.forename: Helen R
authors.initials: HR
authors.lastname: Crooke
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006691:Classical Swine Fever / Q000276:immunology* / Q000517:prevention & control*; D006692:Classical Swine Fever Virus / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology*; D014613:Vaccines, Attenuated; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000939:Epitopes; D014613:Vaccines, Attenuated; D014764:Viral Proteins; D014765:Viral Vaccines; D007371:Interferon-gamma