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ARS Home » Pacific West Area » Pullman, Washington » Animal Disease Research » Research » Publications at this Location » Publication #411002
Research Project: Genetic Approaches and Tools to Prevent, Control, and Eradicate Transmissible Spongiform Encephalopathies

Location: Animal Disease Research

Title: 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

Author
item MAHMOUD, ASMAA - Washington State University
item ABDELLRAZEQ, GABER - Washington State University
item FRANCESCHI, VALENTINA - University Of Parma
item Schneider, David
item Bannantine, John
item FRY, LINDSAY - Former ARS Employee
item HULUBEI, VICTORIA - Washington State University
item DE MATTEIS, GIOVANNA - Crea
item PARK, KUN TAEK - Inje University
item DAVIS, WILLIAM - Washington State University
item DONOFRIO, GAETANO - University Of Parma

Submitted to: bioRxiv
Publication Type: Pre-print Publication
Publication Acceptance Date: 11/21/2023
Publication Date: 11/21/2023
Citation: Mahmoud, A.H., Abdellrazeq, G.S., Franceschi, V., Schneider, D.A., Bannantine, J.P., Fry, L.M., Hulubei, V., De Matteis, G., Park, ., Davis, W.C., Donofrio, G. 2023. 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. bioRxiv. https://doi.org/10.1101/2023.11.20.567939.
DOI: https://doi.org/10.1101/2023.11.20.567939

Interpretive Summary: An effective vaccine is needed to prevent chronic infections in cattle with Mycobacterium avium paratuberculosis (Map), the bacterial agent that causes paratuberculosis or “Johne's disease.” A study was conducted in cattle to determine if a novel virus-based vaccine platform could induce an immune response against Map. The virus-based vaccine was modified to express a major membrane protein of Map after subcutaneous injection. Blood immune cells circulating in cattle after vaccination developed the ability to kill Map in culture experiments. The cell-mediated immune responses observed in this study are thought to be essential to preventing chronic Map infection in cattle through vaccination.

Technical 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 the agent. 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 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'TK-p35NN as a peptide-based vaccine. Subcutaneous vaccination of healthy cattle with BoHV-4A'TK-p35NN elicited a CTL recall response ex vivo. Further studies are warranted to conduct a challenge study to determine if CD8 CTL elicited by vaccination with BoHV-4A'TK-p35NN prevents the establishment of a persistent infection by Map.