Vaccination of cattle with a virus-vectored vaccine against a major membrane protein ofMycobacterium a. subsp.paratuberculosiselicits CD8 cytotoxic T cells that kill intracellular bacteria

Abstract

AbstractInfection of cattle withMycobacterium a. subsp.Paratuberculosis (Map), the causative agent of paratuberculosis, induces an immune response directed toward a 35 kD major membrane protein (MMP) ofMap. CD8 cytotoxic T cells (CTL) are elicited when peripheral blood mononuclear cells from healthy cattle are incubated ex vivo with antigen-presenting cells (APC) primed with bacterial recombinant MMP. Ex vivo development of CTL was MHC-restricted and required the presence of both CD4 and CD8 T cells. The geneMAP2121c,encoding MMP, was modified to express a modified form of MMP (p35NN) in a mammalian cell line, also capable of eliciting an ex vivo CTL response. In the present study, the modified gene for p35NN was placed into a BoHV4 vector to determine the potential use of BoHV-4AΔTK-p35NN as a peptide-based vaccine. Subcutaneous vaccination of healthy cattle with BoHV-4AΔTK-p35NN elicited a CTL recall response, as detected ex vivo. Further studies are warranted to conduct a challenge study to determine if CD8 CTL elicited by vaccination with BoHV-4AΔTK-p35NN prevents the establishment of a persistent infection byMap.