1. Development of an oral vaccine against tuberculosis for use in badgers (Meles meles) Dr Eamonn Gormley, UCD Dublin

2. Transmission of Mycobacterium bovis Environment

3. Badgers in Rep of Ireland ~ 100,000 badgers Tuberculosis is endemic Approx. 50% badgers with tuberculosis in areas associated with chronic cattle TB Approx. 15% badgers with tuberculosis in Areas with no recent history of cattle TB Epidemiological link with infection in cattle Currently controlled by focal reactive culling

4. Enhanced diagnosis of M. bovis infection in badgers With parallel interpretation of culture/histo, infection prevalence approx 50% Diagnostic procedureNo. badgers positive Bacteriology57/132 (43.2%) Histopathology46/132 (34.8%) Gross PM30 /132 (22.7%)

5. Field trial 2009 - 2013 Field Vaccine 2017 Diagnostics 1998 - 2010 Pen studies 2002 - 2013 Registration 2015 - 2019 Applications 2012 - 2016 Vaccine Development Overview

7. Captive Badger BROC facility

8. Badger vaccine studies 1.Developed immuno-diagnostics with AHVLA for Tb in badgers 2. Determined protective efficacy of BCG 3. Tested efficacy of oral BCG vaccine 4 Testing efficacy against natural M. bovis challenge in Field Trial 5 Evaluating AHVLA vaccine candidates for licensing of vaccine

9. Oral vaccination: 10 8 cfu oral vaccine / 10 4 M. bovis challenge 12 week vaccination, 14 week challenge

10. Badger Vaccine Field Trial Principle Objectives Demonstrate BCG is protective in wild badgers under natural transmission conditions Estimate vaccine efficacy Secondary Objectives: Study post-infection vaccination Provide infrastructure for other research – e.g. population dynamics, badger behaviour Address policy / scientific interests

11. Badger Vaccine Field Trial Structure:  Large area: 700 km²  Population: ≥ 300 badgers  Long term study – 3/4 years  TB prevalence ~ 30%

12. Vaccine trial design Area divided into 3 zones 100%, 50% & 0% vaccination 3 year duration Vaccine/placebo blind coded

13. Vaccine trial design 2 sweeps per year Re-vaccinate every 2 nd sweep Monitor population by serology Case definition: M. bovis isolation Initial results in 2014

14. Injectable vs oral vaccine Injectable vaccine Available now! Defined delivery dose Expectations of protection of individual Oral vaccine Needs to be licensed Dose never guaranteed Higher variability However: May be difficult to generate population immunity However: With optimal delivery, can target populations to achieve population immunity

15. For successful vaccination we need fundamental information on badger population structure and epidemiology of Tb transmission What we need to know?

16. Capture zoneInfection prevalence 43.2% 24.2% 14.9% Chronic Tb Std breakdowns Tb free Herds: M. bovis prevalence in badgers spatially clusters with reactor rate

17. M bovis infection in wild badgers: Infection prevalence in social groups * All badgers captured at a main sett during the 11-day capturing period were deemed to belong to the same social group (Griffin et al 2005). Group size*No badgersPrevalence (%) 16744.8 22231.8 31838.9 4850.0 8862.5 9944.4 *All badgers captured at a main sett during the 11-day capturing period were deemed to belong to the same social group (Griffin et al 2005).

18. M bovis infection in wild badgers: Infection status and sex, age, class * The overall prevalence in females (n=77) was 35.1% and in males (n=55) was 54.5%. Sex*Age classBadgers (N=132) % infection FemaleJuvenile1631.3 Adult4141.5 Old2025.0 MaleJuvenile1250.0 Adult3253.1 Old1163.6

19. Who do we vaccinate? Individual badgers - Have some expectation of vaccine effect Social groups - Highest risk of transmission Regional - Targeting populations to achieve ‘herd’ immunity How do we vaccinate? - Develop efficient delivery system

20. When (how often-) do we vaccinate? Individual badgers - duration of immunity Regional - Need to maintain ‘herd’ immunity When do we stop vaccination? If objective is to control the disease in badgers – no endpoint If objective is to eradicate the disease in badgers – finite endpoint

21. Acknowledgements UCD Leigh Corner Denise Murphy Simon More- CVERA Lab staff AHVLA Mark Chambers Glyn Hewinson Sandrine Lesellier CVRL Eamon Costello Lab staff DAFM Margaret Good Anthony Duignan Michael Sheridan James O’Keefe Martin Blake Richard Healy

22. Thank you Photo by: Ian O’Boyle