Scientists at the University of Surrey in the U.K. have developed a novel vaccine and complementary skin test to protect cattle against bovine tuberculosis (TB).
Publishing their findings in the journal Scientific Reports, the researchers reported that they have, for the first time, created a vaccine that is compatible with a synthetic form of the tuberculin skin test (PPD) -- a legally required test used for bovine TB surveillance throughout the U.K., where the cattle industry has been facing a long-running bovine TB outbreak.
Bovine TB is an infectious disease in cattle that affects their lungs, and those that test positive for the disease are culled. According to the University of Surrey, the BCG vaccine -- which is currently used to protect humans against TB and is effective in cattle -- is incompatible with the PPD test.
Cattle that are vaccinated with the BCG vaccine, which contains a harmless strain of the bovine TB pathogen Mycobacterium bovis, produce a positive PPD test for TB, making it impossible to distinguish -- with the PPD skin test -- if the animal has TB or has simply been vaccinated, the university explained. Vaccinating cows with BCG is, therefore, banned in most countries in the world, enabling veterinarians to continue to use the PPD skin test to diagnose the disease in cattle.
During this study, the Surrey researchers sought to make a new BCG vaccine strain that lacks some of the proteins shared with the M. bovis pathogen by identifying genes that contain encoded immunogenic proteins that could be removed from BCG without affecting its ability to work as a live vaccine, the announcement said.
To do this, a collection of BCG strains that had each lost a single gene were injected into cows, and survival rates were measured. This allowed the team to identify genes that could be removed without compromising the BCG vaccine’s effectiveness.
These dispensable genes encoding immunogenic proteins were then deleted from the BCG chromosome to make a BCG-minus strain. The deleted immunogenic proteins were used to develop a new synthetic skin test that, like PPD, will be positive for animals that have been exposed to TB but, unlike PPD, will be negative for animals that have been vaccinated with the BCG-minus strain, the researchers explained.
The protective efficiency of the new strain was tested in guinea pigs, the announcement said, and it was found that TB-infected guinea pigs tested positive for the disease using the synthetic skin test, while guinea pigs vaccinated with the BCG-minus strain did not. So, unlike PPD, the new skin test also works in animals that are protected from TB by BCG-minus vaccination. This potentially allows farmers and veterinarians to protect their animals with the new BCG vaccine while still maintaining a diagnostic test that will detect TB.
“In order to control the spread of bovine TB, effective vaccination and accurate early diagnosis of the disease are critical. This new vaccine provides protection against bovine TB and will help in the fight against this deadly disease, which infects over 50 million cattle worldwide and is economically devastating to farmers," University of Surrey professor of molecular genetics Johnjoe McFadden said.
“The next stage of our work will be to demonstrate that both the synthetic skin test and BCG-minus vaccine work in cattle herds. If they do, then it will be possible to vaccinate cattle against TB yet retain the value of the skin test for diagnosis," McFadden added.
This study was done in partnership with the U.K.'s Animal & Plant Health Agency, Public Health England, the Translational Research Platform for Veterinary Biologicals in Chennai, India, and HPC-Medical & Bioinformatics Applications Group in Puna, India.