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Continued Vaccine Development: Improving BCG and Developing Non-Sensitising Vaccines for Cattle

Institutions
Veterinary Laboratories Agency, UK
Start date
2012
End date
2016
Objective
  1. Development of vaccination strategies that improve the duration of immunity of BCG in cattle.
  2. Development of vaccines that do not sensitise cattle to the single intradermal comparative tuberculin test (non-sensitising vaccines).
  3. Identification of biomarkers that identify cattle protected against M. bovis infection.
  4. Screening novel vaccine candidates in mice to prioritise vaccines for testing in the bovine challenge model.
  5. Co-ordinating collaboration with the human TB vaccine programme.
More information

The 1997 ‘Krebs’ report recommended the development of TB vaccines for cattle and badgers, and a diagnostic test to differentiate infected from vaccinated cattle. Since then total investment by Defra in cattle vaccine development has now reached around £18m.

Vaccination of cattle against TB could help reduce the number of TB herd breakdowns and their severity by reducing the rate and the consequences of infection from cattle or badgers to susceptible cattle and its onward transmission. Therefore alongside other control measures, vaccination has the potential to make a significant contribution to the control and eventual eradication of bovine TB.

However, the primary candidate vaccine against TB in cattle, BCG, is not 100% effective and a proportion of vaccinated animals may still become infected. Recent research also indicates that the duration of BCG induced immunity is between 1 and 2 years for cattle.

Under current trade rules, vaccination with BCG would also have an impact on the ability to trade live cattle and cattle products, such as milk. This is because the current BCG-based vaccine under development in cattle can interfere with the primary diagnostic test, the tuberculin skin test, producing false-positive results in vaccinated (but uninfected animals). Under current rules animals testing positive to this test would have to be slaughtered or re-tested, they would not be eligible for trade and their herds of origin would lose their officially TB free (OTF) status.

Therefore, in parallel to the vaccine, a diagnostic test has been developed to differentiate infected from vaccinated animals (“DIVA” test), that could be used alongside the tuberculin skin test for cattle that remain sensitised to the skin test (for most animals sensitisation is transient and will disappear within 6 - 9 months of vaccination).

This project builds and extends on significant progress made over the last decade in the development of TB vaccines for cattle and addresses key policy requirements that arise from the short duration of immunity induced in cattle by BCG.

First, we will determine whether annual revaccination of cattle with BCG can maintain sufficient levels of protection over time. We will also test if re-vaccination with BCG results in re-sensitisation of vaccinated animals to the tuberculin skin test and whether the DIVA test can still be used in the face of a number of rounds of BCG vaccination and tuberculin skin testing. We will also investigate whether novel vaccination regimes can be developed to improve and extend BCG-induced protection against M. bovis infection and whether the lead subunit vaccine candidates identified in SE3224 can be used to boost and extend the duration of BCG-induced immunity without sensitising animals to the tuberculin skin test.

Our second main objective is to develop vaccines that do not sensitise cattle to the tuberculin test. This would allow the continuation of existing tuberculin skin test-based test and slaughter strategies alongside vaccination and is the approach to vaccine development favoured by stakeholders and the EU.

The expected outcomes of this project will be to optimise the way BCG vaccination should be applied in cattle, to improve its efficacy and to develop vaccines that, whilst effective, do not sensitise vaccinated animals to the tuberculin skin test.

Funding Source
Dept. for Environment, Food and Rural Affairs
Project source
View this project
Project number
SE3266
Categories
Bacterial Pathogens
Chemical Contaminants