Development of an oral vaccine against tuberculosis for use in badgers (Meles meles)

Dr Eamonn Gormley, UCD Dublin

Transmission of Mycobacterium bovis

Environment

Badgers in Rep of Ireland

~ 100,000 badgers

Tuberculosis is endemic

Approx. 50% badgers with tuberculosis inareas associated with chronic cattle TB

Approx. 15% badgers with tuberculosis inAreas with no recent history of cattle TB

Epidemiological link with infection in cattle

Currently controlled by focal reactive culling

Enhanced diagnosis of M. bovis infection in badgers

With parallel interpretation of culture/histo, infection prevalence approx 50%

Diagnostic procedure No. badgers positive

Bacteriology 57/132 (43.2%)

Histopathology 46/132 (34.8%)

Gross PM 30 /132 (22.7%)

Field trial2009 - 2013

Field Vaccine

2017

Diagnostics1998 - 2010

Pen studies2002 - 2013

Registration2015 - 2019

Applications2012 - 2016

Vaccine Development Overview

Captive Badger BROC facility

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

Oral vaccination: 108 cfu oral vaccine / 104 M. bovis challenge

12 week vaccination, 14 week challenge

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

Badger Vaccine Field Trial

Structure:

Large area: 700 km²

Population: ≥ 300 badgers

Long term study – 3/4 years

TB prevalence ~ 30%

Vaccine trial design

• Area divided into 3 zones

• 100%, 50% & 0% vaccination

• 3 year duration

• Vaccine/placebo blind coded

Vaccine trial design

• 2 sweeps per year

• Re-vaccinate every 2nd sweep

• Monitor population by serology

• Case definition: M. bovis isolation

Initial results in 2014

Injectable vs oral vaccine

Injectable vaccine

Available now!

Defined delivery dose

Expectations of protectionof individual

Oral vaccine

Needs to be licensed

Dose never guaranteed

Higher variability

However:

May be difficult to generatepopulation immunity

However:

With optimal delivery, can target populations to achieve population immunity

For successful vaccination we need fundamental

information on badger population structure and

epidemiology of Tb transmission

What we need to know?

Capture zone Infection prevalence

43.2%

24.2%

14.9%

Chronic Tb Std breakdowns Tb freeHerds:

M. bovis prevalence in badgers spatially clusters with reactor rate

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 badgers Prevalence (%)

1 67 44.8

2 22 31.8

3 18 38.9

4 8 50.0

8 8 62.5

9 9 44.4

*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).

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 class Badgers (N=132)

% infection

Female Juvenile 16 31.3

Adult 41 41.5

Old 20 25.0

Male Juvenile 12 50.0

Adult 32 53.1

Old 11 63.6

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

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

Acknowledgements

UCDLeigh CornerDenise MurphySimon More- CVERALab staff

AHVLAMark ChambersGlyn HewinsonSandrine Lesellier

CVRLEamon CostelloLab staff

DAFMMargaret GoodAnthony DuignanMichael SheridanJames O’KeefeMartin BlakeRichard Healy

Thank you

Photo by: Ian O’Boyle