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Sci Adv. 2019 Jul 17;5(7):eaax4899. doi: 10.1126/sciadv.aax4899. eCollection 2019 Jul.

A defined antigen skin test for the diagnosis of bovine tuberculosis.

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Department of Animal Sciences, Pennsylvania State University, University Park, PA, USA.
The Huck Institutes, Pennsylvania State University, University Park, PA, USA.
Animal and Plant Health Agency, Surrey, UK.
Cisgen Biotech Discoveries, Chennai, India.
Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia.
Independent Researcher, Lelystad, Netherlands.
Bill and Melinda Gates Foundation, Seattle, WA, USA.
World Organization for Animal Health, Paris, France.
Centre for Bovine Tuberculosis, Institute for Biological, Environmental and Rural Sciences, University of Aberystwyth, Aberystwyth, UK.


Bovine tuberculosis (bTB) is a major zoonotic disease of cattle that is endemic in much of the world, limiting livestock productivity and representing a global public health threat. Because the standard tuberculin skin test precludes implementation of Bacille Calmette-Guérin (BCG) vaccine-based control programs, we here developed and evaluated a novel peptide-based defined antigen skin test (DST) to diagnose bTB and to differentiate infected from vaccinated animals (DIVA). The results, in laboratory assays and in experimentally or naturally infected animals, demonstrate that the peptide-based DST provides DIVA capability and equal or superior performance over the extant standard tuberculin surveillance test. Together with the ease of chemical synthesis, quality control, and lower burden for regulatory approval compared with recombinant antigens, the results of our studies show that the DST considerably improves a century-old standard and enables the development and implementation of critically needed surveillance and vaccination programs to accelerate bTB control.

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