New tuberculosis tests pave way for cow vaccination programs

"Tuberculosis kills more people in the world than any other infectious disease – in fact, three people die every minute of this disease," said Vivek Kapur, professor of microbiology and infectious diseases and Huck Distinguished Chair in Global Health. at Penn State. "What is less well known is that cattle in many low- and middle-income countries are not only infected with tuberculosis and suffer terribly, but they are also important reservoirs for the transmission of the disease to humans. man through the consumption of unpasteurized milk or dairy products and cohabitation with infected animals. "

The team created their tests – described in the July 17 issue of Progress of science – by targeting specific proteins, previously identified by scientists from Denmark and the United Kingdom, which are absent or not secreted by the widely used vaccine strain, called BCG. The ability to express these proteins was lost when the bacterium was adapted for use as a vaccine more than a hundred years ago. By indicating the presence or lack of reactivity to these "missing" proteins, new tests distinguish an infected animal from the natural form of the disease of another who has been vaccinated.

"Our diagnostic reagent is a simple badtail of synthetic peptides representing antigens found in natural TB bacteria but not recognized by the immune system after BCG vaccination," said Sreenidhi Srinivasan, graduate student in molecular, cellular and integrative biosciences. at Penn State. . "These antigens, when applied to the skin, cause an immune response in cows with tuberculosis, whereas no reaction occurs in BCG vaccinated animals."

The publication also highlights a promising alternative baday format based on a recombinant fusion protein whose performance is comparable to that of the peptide badtail. This protein has been developed to make the UK government compatible with its potential livestock vaccination program, although the peptide-based test potentially removes regulatory hurdles in countries that impose stricter restrictions on their use. use of products from genetically modified organisms.

The team evaluated the utility of its test in cattle in the United Kingdom, Ethiopia and India.

"It worked out well, exceeding the performance of the traditional test by clearly differentiating vaccinated cattle from infected animals," Kapur said.

Kapur noted that the BCG vaccine, which was developed in the early 1900s from the bacteria that causes the disease in cattle and is the most widely used vaccine in humans, has remained largely unused in humans. cattle because of the risk of complication of the diagnosis. In fact, the European Union, the United States and many other countries prohibit its use in cattle mainly for this reason.

"While BCG rarely confers sterilizing immunity to humans or livestock, it has been shown to be effective in preventing a significant number of infections and protecting against more severe forms of human tuberculosis", did he declare. "However, the inability to know if a cow has the disease or has just been vaccinated has prevented governments from implementing cow vaccination programs, leaving animals and humans vulnerable to infection. "

Instead of vaccinating cattle, many countries have used a "test and slaughter" approach to control TB in these animals. This highly effective method effectively eliminated tuberculosis in the United States almost 100 years ago and is still used in high-income countries around the world. Unfortunately, testing and slaughtering are still impossible in most low- and middle-income countries, where small and marginal cattle owners can not afford to lose what is often their main source of income and nutrition. . In addition, in some countries, such as India, slaughtering livestock is illegal because of its cultural and spiritual importance.

Treating cows infected with tuberculosis with antibiotics is not feasible either. While humans who contract TB can often be treated – as long as they do not contract an antibiotic-resistant strain – treating cows with antibiotics is expensive and can take them out of their milk supply service, sometimes for long periods of time. years.

"The new diagnostic test we have developed could replace the current standard test, used for nearly a century now," Srinivasan said. "In addition to being economical and easy to manufacture and standardize quality control, new tests allow for reliable differentiation between infected and vaccinated animals, which is one of the main limitations of the current method." Access to such tests paves the way for vaccination as an intervention strategy in contexts where testing and killing strategies are not affordable for socio-economic reasons. "

Laurel Easterling, animal science student at Penn State; Maroudam Veerasami, Director, Cisgen Biotech Discoveries Private Limited; Gareth Jones, Sabine Steinbach and Thomas Holder, Researchers, Animal and Plant Health Agency, United Kingdom; Martin Vordermeier, Team Leader, Animal and Plant Health Agency (UK) and Professor of Immunology at the University of Aberystwyth (United Kingdom); Aboma Zewude, Veterinary Laboratory Technologist, Adis Ababa University, Ethiopia; Abebe Fromsa, badociate professor and Gobena Ameni, professor at the Institute of Pathobiology Aklilu Lemma of the University of Addis Ababa (Ethiopia); Douwe Bakker, Technical Consultant, Lelystad, the Netherlands; Nicholas Juleff, Senior Program Officer, Bill & Melinda Gates Foundation; Glen Gifford, Project Manager, World Organization for Animal Health (OIE), France; and R.G. Hewinson, President Sêr Cymru, University of Aberystwyth, United Kingdom.

The Bill & Melinda Gates Foundation, as well as the Ministry of the Environment, Food and Rural Affairs (Defra) and the UK Department for International Development supported this research.