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Be a DIVA: Exploring a new strategy to prevent Johne’s disease

Contributed by Cari Reynolds Published on 09 September 2020

The economic impact of Johne’s disease on the dairy industry rivals that of clinical mastitis. In the U.S., well over $250 million each year is lost due to reduced milk production, premature culling and reduced reproductive efficiency.

The causative agent of Johne’s disease is Mycobacterium avium subsp. paratuberculosis (MAP), a resilient, slow-growing bacteria that is not only prevalent in dairy cattle but also in numerous wildlife reservoirs, with transmission possible between both domestic and wild species. The physiological effects of Johne’s disease on an infected animal result in high morbidity and considerable economic impact to a producer. It is likely that MAP infection can occur in utero or within the first six months of life, and youngstock are highly susceptible. Johne’s disease targets the intestinal tract, which results in inflammation, enteritis and subsequent issues with absorption and feed efficiency. Many infected animals may not develop clinical signs, but subclinical infection can still have detrimental effects on productivity, and the animal can still shed bacteria into the environment through fecal material. Johne’s disease has also been linked to Crohn’s disease in humans. While there is no definitive evidence to support this connection, it is still considered a public health risk to consumers due to its presence in milk and the ability of some strains of MAP to evade pasteurization.



Numerous challenges face the management and prevention of MAP infection in cattle, mainly due to its ease of transmission, its prevalence in the environment, the lack of reliable diagnostic testing and the lack of a preventative vaccine. The most common diagnostic tests used to detect Johne’s disease are fecal culture with polymerase chain reaction (PCR) and serum ELISA. However, these tests can have varying sensitivities, which can lead to false positive or false negative results. If the sensitivity of the test is low, it is possible that the prevalence of MAP can be underestimated. These tests are also not cost-effective nor readily available to producers and require veterinary oversight to perform and interpret. An ideal alternative to diagnostic testing is the development of vaccines that prevent persistent infection rather than only reduce clinical symptoms. The one Johne’s disease vaccine for cattle licensed in the U.S. (Mycopar) was under restricted use due to human health risks and could only be administered by a Johne’s disease-certified veterinarian. The discontinuation of Mycopar in 2019 further propagated the need for a widely available and preventative Johne’s disease vaccine, an urgent research gap that has attracted the attention of scientists.

Research at the University of Calgary aimed to address this gap by evaluating a vaccine development strategy that could provide long-term protection against Johne’s disease. The research sought to evaluate cellular immune responses in animals injected with a strain of MAP modified to create marker-specific immune responses. This type of approach is known as attenuation, where a strain of a pathogen is genetically encoded to remove harmful virulence factors but maintain or include those properties which stimulate an immune response. Immune markers are used to detect and measure immune responses to a certain antigen, and their identification is essential to understanding immune function. In this study, calves were injected with a wild-type strain of MAP, the modified MAP strain or a placebo. When blood samples from these calves were challenged with a Mycobacterium avium antigen, calves that received both the wild-type strain and the modified strain exhibited strong interferon gamma (IFN-γ) release, which is an indicator of a positive cellular immune response. The modified MAP strain also caused a better immune response than the wild-type strain. The researchers were successful in developing a marked strain of MAP, which could be further studied in order to take the next step toward developing a vaccine. The authors also indicated that the long-term goal was to develop a vaccine strain of MAP that would allow for differentiation between infected and vaccinated animals (DIVA). More work remains to further evaluate this approach, but a live attenuated vaccine for Johne’s disease would be a considerable step toward its control and potential eradication.

So, what are the benefits to attenuated vaccines? These types of vaccines are not uncommon; the intranasal influenza vaccine for humans is a live attenuated vaccine, as are the chicken pox, rotavirus and the MMR (measles, mumps, rubella) vaccines. Their advantage is that they are relatively easy to produce, and they induce a more robust immune response than other types of vaccines. Since the disease-causing strain of a bacteria or virus is used in the development, inserting different genetic codes allows for an immune response that mimics that of natural infection. In the case of using this approach for prevention of Johne’s disease, studies in goat and calf models showed that using attenuated strains of MAP in vaccines resulted in less fecal shedding of bacteria, which would greatly reduce transmission and recurrent infection in herds. While more work remains to be performed, this research holds great promise toward mitigation of Johne’s disease.  end mark

References omitted but are available upon request. Click here to email an editor. 

This first appeared in the Miner Institute Farm Report June 2020 newsletter.


Cari Reynolds
  • Cari Reynolds

  • Agricultural Research Ph.D. student
  • William H. Miner Agricultural Research Institute
  • Email Cari Reynolds