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.

doi:10.1101/2023.11.20.567939

bioRxiv · 10.1101/2023.11.20.567939

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.

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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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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.. 2023-11-21. 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. https://doi.org/10.1101/2023.11.20.567939

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