Journal Article

Characterisation of vaccine-induced, broadly cross-reactive IFN-γ secreting T cell responses that correlate with rapid protection against classical swine fever virus

Johns, Helen L., Graham, Simon P., Everett, Helen E., Sosan, Olubukola, Haines, Felicity J., La Rocca, S. Anna, Rümenapf, Till, Crooke, Helen R., Lamp, Benjamin

2012

Overview

► Vaccine-induced T cell IFN-γ responses show broad reactivity against CSFV strains. ► T cell epitopes are conserved between CSF and BVD viruses. ► Well conserved antigenic peptides mapped on E2 and NS3 proteins. ► IFN-γ exerts anti-viral effects on CSFV in vitro. 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.

• Publisher: Elsevier Ltd
• Subject: Allergy and Immunology / Amino Acid Sequence / Animals / Antibodies / antiviral properties / Bovine viral diarrhea virus / CD4 antigen / CD8 antigen / CD8-positive T-lymphocytes / Classical Swine Fever - immunology / Classical Swine Fever - prevention & control / Classical swine fever virus / Classical swine fever virus - immunology / Colony-stimulating factor / cross reaction / Cross Reactions - immunology / Cross-reactivity / Cytotoxicity / Data processing / development aid / Epitopes - chemistry / Epitopes - immunology / gamma -Interferon / genotype / Genotypes / Hog cholera / immunologic techniques / interferon-gamma / Interferon-gamma - immunology / Interferon-gamma - secretion / Interferon-γ / Kinetics / Lymphocytes T / Male / Molecular Sequence Data / NS3 protein / Peptide libraries / Peripheral blood / proteins / Serological tests / Swine / T-cells / T-Lymphocytes - immunology / Vaccination and infection / Vaccines / Vaccines, Attenuated / Viral Proteins - chemistry / Viral Proteins - immunology / Viral Vaccines - immunology / viruses