Conclusions
Researchers have now looked for vaccine and diagnostic antigens using proteomic approaches for at least 35 years. Although there are promising antigens that have been discovered and newer technologies to increase sensitivity or amplify signal, there is a real barrier getting these incorporated into marketable tests and vaccine formulations to control paratuberculosis or at least help the animal producer make informed decisions about herd management.
There may never be an antigen that provides sterile immunity or predicts infection with 99% accuracy, but that shouldn't dissuade researchers from examining ways to improve upon what is currently available. Trends from the past 15 years show that paratuberculosis incidence is on the rise, with 68% of US dairy herds having at least one infected cow reported in the 2007 National Animal Health Monitoring System (NAHMS) dairy survey to over 90% in 2014 from NAHMS dairy 2014. Thus, it is critical to maintain the search for the best tools to fight this disease.In the course of assembling this chapter a few proteins appeared noticeably in many studies. These include the AhpC, FAP and DnaK proteins, among others. Their repeated appearance may perhaps suggest that they are abundant in the bacilli more than being immunogenic or useful for vaccination. This might be the case for DnaK in particular, which is present in nearly all proteomic preps and is abundantly expressed in MAP. FAP (a.k.a. ModD) is a rare MAP protein that acts as a strong B-cell antigen (Li et al., 2017a; Li etal., 2017b), T-cell antigen (Lee etal., 2009) and an activator of dendritic cells that interacts with TLR-4 (Noh et al., 2012). Therefore, perhaps these three and a handful of other antigens, such as PtpA, appear to be the best targets to focus on in the future.
And finally, despite heroic efforts by MAP researchers around the world, the diagnostics for paratuberculosis is still at a state where (i) we cannot confidently certify a healthy appearing animal as not infected with MAP, and (ii) we cannot confirm MAP infection in an animal that does not show overt signs of disease. While this does not seem encouraging, testing has improved to a point where herd-level infections, or lack thereof, are confidently captured. In general, paratuberculosis ELISA test sensitivity and specificity has increased over time.
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