The recently published article describing the discovery of a MAP mutation that may lead to the development of a MAP vaccine for both animals and humans was received by our community with great interest. One of the researchers, Dr. William C. Davis, has provided Human Para with a summary of this highly technical article. A huge thanks to Dr. Davis and his colleagues for this piece, and for their contribution to MAP science.
"The results at this stage of our studies are very promising. The finding that deletion of a single gene cripples Map’s ability to establish a persistent infection led to the discovery of a peptide with potential for development of a peptide-based vaccine. Studies with the peptide in tissue culture show vaccination leads to development of immune cells that can kill Map inside macrophages, an essential requirement for a vaccine against intracellular pathogens. While this is being investigated in cattle, it could have implications for human health as well."
Research Summary said...https://vmp.vetmed.wsu.edu/people/faculty/profile/william-c-davishttps://www.feedstuffs.com/nutrition-health/map-protein-may-aid-battle-against-johnes-disease
The long term objectives of our research program are to elucidate the mechanisms regulating the immune response to infectious agents and develop protective vaccines. To achieve these objectives, we continue to develop and use monoclonal antibodies and assays to study the immune response in domestic animals with a primary focus on ruminants. M. avium subsp. Paratuberculosis (Map) has been selected as the model pathogen for our investigations because of its economic importance and its potential for providing insight into the mechanisms regulating the immune response to Map and other intracellular pathogens. Map is the causative agent of Johne’s disease (JD) in cattle, a chronic wasting disease of the intestine. It causes significant economic loss to producers, especially the dairy industry, due to increase in forage consumption, decreased milk production and early culling due to poor health of affected animals. There is also a concern that Map is a zoonotic pathogen. Map has been isolated from human patients with Crohn’s disease (CD), a chronic inflammatory disease of the intestine. It is not clear whether Map is the etiologic agent causing Crohn’s disease. However, recent studies on CD and mycobacterial pathogens M. tuberculosis (Mtb) and Map have shown a similarity in the mechanisms of pathogenesis at the cellular and molecular level. The studies have revealed the cross regulation of the immune system by regulatory T cells and effector T cells mediating protective immune responses is dysregulated, giving rise to an imbalance that results in chronic inflammation of target tissues, and in the case of Mtb and Map dysregulation of protective immunity. To extend these observation we developed a bovine cannulated ileum model to conduct studies on the mechanisms of pathogenesis mediated by Map in the natural host, studies that cannot be conducted in humans. The model has offered an opportunity to study the interaction of Map during the early and late stages of infection. We have also developed and used a flow cytometric assay to analyze the immune response to Map and methods to elucidate the functional changes associated with dysregulation of the immune system. Use of these methods in conjunction with development of methods to monitor the intracellular killing of bacteria by cytotoxic T cells have facilitated analysis of the functional activity of cytotoxic T cells responding to Map and derived candidate antigens. Ongoing studies with a mutant of Map, with a deletion in relA, has shown deletion abrogates the capacity of the mutant to establish a persistent infection. Further studies have shown the target of the immune response is directed towards a membrane protein (MMP). Ex vivo studies have shown stimulation with the MMP leads to the development of cytotoxic T cells with the capacity to kill intracellular bacteria. This major finding indicates a peptide based vaccine is possible against a major pathogen. These findings will now be used to advance our studies to the next phase, development and validation of a virus vector containing the gene encoding the MMP as a vaccine for JD.
Post Edited (xy123) : 7/12/2019 12:30:25 PM (GMT-6)