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USDA scientists develop a promising new vaccine for Johne’s disease

Judy Stabel for Progressive Dairy Published on 16 September 2021

Do you have Johne’s disease in your dairy or beef cattle herd?

If so, you may be seeing signs of clinical disease in some of your cows such as, severe diarrhea that can’t be resolved with antibiotics, significant weight loss even though animals are still making their way up to the feedbunk and a swelling of soft tissue under the jaw known as submandibular edema, which occurs in very late stages of the disease. Johne’s disease (also known as paratuberculosis) is a chronic, progressive intestinal disease in ruminants caused by infection with Mycobacterium avium subsp. paratuberculosis (MAP). Generally, animals become infected as neonates, often in the maternity pen, when calves have direct contact with an infected dam shedding MAP into her feces and milk. The disease manifests itself over a period of years and is precipitated by stressors, such as calving, lactation, environmental conditions and poor nutrition. Unfortunately, if you are seeing these clinical signs in a few animals, many more cows within the herd may be infected but asymptomatic. The prevalence within the herd will increase economic losses for producers as infection impacts fertility, milk production and susceptibility to infections with other pathogens. Recent evidence suggests that over 90% of U.S. dairy herds have some level of infection within the herd; however, accurate numbers are not available for the level of prevalence in U.S. beef herds. The increasing prevalence of paratuberculosis supports the need for new efficacious vaccines, especially a vaccine that does not interfere with diagnostic testing for bovine tuberculosis (bovine TB), a regulated disease.

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Vaccination has been successfully used as a management tool for many infectious diseases in cattle and other ruminants, including Johne’s disease. Vaccination has reduced fecal shedding of MAP, reduced clinical signs in infected animals and may reduce incidence of disease within herds. Historically the only vaccine available for sale in the U.S. was Mycopar, which was a whole-bacterium heat-killed vaccine. Mycopar was used most widely in dairy herds in the U.S. and was successful in reducing the prevalence of disease within herds. However, some drawbacks to the vaccine were evidence of severe inflammation and granuloma formation at the injection site (usually in the brisket), which could downgrade profits at the sale barn or at slaughter. The vaccine also interfered with bovine TB skin testing and was unable to distinguish between MAP-infected cattle and those that got vaccinated. The development of new vaccines based upon specific proteins of the MAP bacterium seemed a promising avenue of research that could lead to an improved product.

Recently, USDA Agricultural Research Service (ARS) Scientists, myself and John Bannantine, published research on the development and testing of a new vaccine for Johne’s disease. The vaccine is composed of four recombinant MAP proteins that had previously been found to be protective in a mouse infection model and had also demonstrated reactivity in serum from naturally infected dairy cows, suggesting that the four proteins were strong antigens.

Two studies were conducted with dairy calves to see if vaccination would protect against infection after calves were challenged with the live bacteria (MAP). The first study was a pilot study with eight calves, four vaccinated and four not vaccinated. All calves were challenged with live MAP for a 12-month period, during which blood and fecal samples were taken and analyzed. At the end of the study period, the calves were necropsied for tissues to evaluate tissue colonization. The second study followed the exact same protocol, except we added more calves and looked at low and high doses of the vaccine.

Both studies demonstrated that the vaccine was able to lower intestinal colonization of the bacterium and reduce shedding of the bacteria in the feces, with improved results observed for the higher dose of vaccine. This is good news as it suggests that vaccinated cows would be less likely to spread the infection to their calves and to other cows in the herd if they were exposed to the bacterium. Additionally, vaccinated calves had higher levels of pro-inflammatory cytokines in their blood, an indication of protective immunity.

Now that pilot studies have been completed, what is needed are field studies to prove efficacy of the vaccine in dairy and beef herds. For that to be accomplished, collaborative studies with an industry partner and dairy/beef producers would be necessary. An industry partner would have the capability of scaling up production of the vaccine, providing enough product to engage multiple herds to get the best data possible. Since the Mycopar vaccine is no longer available, new vaccines are critical for producers to manage this stealthy disease in their herds. Clearly, a safe and efficacious vaccine is needed that not only prevents infection but also eliminates shedding of MAP through feces, colostrum and milk to curtail the spread of infection. We are hopeful that this vaccine candidate will be the one that provides that level of protection for livestock and reassurance for producers.  end mark

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PHOTO: Staff photo.

Judy Stabel is the lead scientist of the Johne's Disease Research Project at the USDA-ARS National Animal Disease Center. Email Judy Stabel.

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