Vaccination of cattle with a virus-vectored vaccine against a major membrane protein of Mycobacterium a. subsp. paratuberculosis elicits CD8 cytotoxic T cells that kill intracellular bacteria
Mahmoud, A. h. A.; gabdellrazeq, G. s.; Franceschi, V.; Schneider, D. A.; Bannantine, J. P.; Fry, L. M.; Hullubei, V.; Demattis, G.; Park, K.-T.; Davis, W. C.; Donofrio, G.
Show abstract
Infection of cattle with Mycobacterium a. subsp. Paratuberculosis (Map), the causative agent of paratuberculosis, induces an immune response directed toward a 35 kD major membrane protein (MMP) of Map. 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 gene MAP2121c, 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-4A{Delta}TK-p35NN as a peptide-based vaccine. Subcutaneous vaccination of healthy cattle with BoHV-4A{Delta}TK-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-4A{Delta}TK-p35NN prevents the establishment of a persistent infection by Map.
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