2017 MAP Conference: Implication of MAP Infection in Cattle with Implications for Infection in Humans
by Dr. William C. Davis
Appearing by WebEx at the conference, Dr. Davis is a researcher and professor in the Department of Veterinary Microbiology and Pathology at Washington State University. Here, he summarizes the findings from his 27 year MAP study and provides an update on his progress in developing a cattle vaccine for MAP that may have insights into human MAP as well.
Q&A With Dr. Davis
Why have the MAP vaccines for animals been less than effective or not worked thus far?
The challenge to making a vaccine to MAP is the same as the challenge to making a vaccine to M. tuberculosis. The use of killed vaccines over the past few years has shown there is a potential of developing a vaccine. Vaccination leads to the development of an immune response that is partially protective. It reduces the number of infected animals that progress to clinical disease, but the immune response elicited by the killed vaccine doesn’t prevent establishment of a persistent infection.
Until now understanding of the immune system in cattle has been limited. Monoclonal antibody reagents similar to those made in humans had to be developed and characterized. Sufficient progress has now been made to study the immune response to MAP and methods to test candidate vaccines for efficacy. Our strategies have allowed us to identify a MAP gene that is the Achilles heel of MAP. When deleted, it disrupts the mechanisms used by MAP to establish a persistent infection. Our most recent studies show that the mutant elicits a cell mediated immune response that clears infection. Studies in culture show cytotoxic T cells develop that are able to kill intracellular MAP. The immune response is directed towards a membrane protein. Studies being completed, at present, show the cytotoxic T cells can be generated in a tissue culture system.
Live, attenuated vaccines have been effective for viral infections. We have obtained evidence that a live attenuated vaccine would work in cattle, but it is difficult to get a live attenuated vaccine on the market. The identification of a membrane protein that elicits the same immune response overcomes this difficulty. We are now at a point where resources are needed to validate a peptide-based vaccine using the MAP protein and methods of delivery.