Development of Vaccine Approaches for Bovine Tuberculosis in Free-Ranging White-tailed Deer

Mitchell Palmer, Ray Waters, Tyler ThackerNational Animal Disease Center, ARS, USDA

Ames, IA

Wildlife Vaccines

• Public health: rabies, plague, Lyme disease

• Livestock production: bovine TB, brucellosis, pseudorabies

• Iconic or endangered species: pasteurellosis (Bighorn sheep), anthrax (Black rhino)

Wildlife Vaccines-Challenges-

• Multiple species in natural transmission cycle

• Effective oral vaccine

• Safety of non-target species

• Fastidious feeding behavior

• Instability of vaccine in prevailing environmental conditions

• High reproductive rates and population turnover

• Requirement for low unit cost

– Government funding (development, purchase, delivery)

Agent

• Mycobacterium tuberculosis complex> 99.95% sequence homology

• M. tuberculosis• M. bovis – broadest host range• M. caprae• M. africanum• M. canetti• M. microti• M. pinnipedii• M. mungi

Cattle are often the original

source of M. bovis in wildlife.

As the prevalence of bovine tuberculosis

decreases in livestock, the relative

importance of wildlife reservoirs

increases.

Tuberculosis Eradication

• 1900- tuberculosis leading cause of death

– 10-25% of human tuberculosis due to M. bovis

• 1917- USDA eradication program

– 15,000 deaths to M. bovis

– 3x- number of foodborne deaths today

• Current surveillance is slaughter surveillance

Obstacles to Bovine Tuberculosis Eradication

• Importation of infected cattle– Need rapid, reliable and inexpensive test to at border crossings.

• Inability to Test and Remove Cattle– Need reliable, accurate tests to remove infected cattle without

whole herd depopulation.

• Wildlife Reservoirs– Need for vaccines for wildlife.

• Safe vaccines• Vaccine delivery systems

– Need for vaccines for cattle.• Infected vs Vaccinated

Tuberculosis in Wildlife• Traditional eradication methods used for livestock DO

NOT work with wildlife reservoirs.

• No country with an established wildlife reservoir of tuberculosis has successfully eradicated tuberculosis from domestic livestock.

• Vaccines viewed as possible control measure.

Mycobacterium bovis bacille Calmette-Guerín (BCG)

• BCG was developed 1906-1919.

• Originally isolated from a cow.

• Continuous passage led to decreased virulence

• Oldest of vaccines in use today.

• World’s most widely used vaccine (3 billion doses since 1920).

• Vaccinated individual may have positive skin test.

Albert CalmetteCamille Guerin

Vaccination in the US

Efficacy

Does vaccination prevent infection?

Does vaccination prevent disease (lesion development)?

Does vaccination decrease transmission?

Stage 1 Stage 2

Stage 3 Stage 4

Medial retropharyngeal LN

Total Score

Medial retropharyngeal LNBCG Danish: no lesionsBCG Pasteur and non-vaccinates: Stages I-V

LungBCG Danish: Stages I-IIIBCG Pasteur: Stages I- IIINon-vaccinates: Stages I-IV

Mediastinal LNStage I Stage II Stage III Stage IV Total

Oral 0 0 0 0 0

Oral Bait 0 0 0 0 0

Parenteral 4 0 11 3 18

Non-vaccinated 18 2 8 18 46

LungStage I Stage II Stage III Stage IV Total

Oral 0 0 0 0 0

Oral Bait 0 0 0 0 0

Parenteral 12 5 2 6 25

Non-vaccinated 6 8 20 15 49

Oral vaccination of white-tailed deer with M. bovis BCG

Vaccinates Non-vaccinates

Gross Lesions 2/17 11/16

Microscopic Lesions 4/17 11/16

M. bovis isolation 5/17 9/16

Number of tissues 8 22

Med retro LN I II III IV

Vaccinates 9 0 0 0

Non-vaccinates 26 9 5 11

Is it safe?

• Adverse reactions

• Non-target species

• Public health concerns– Possible exposure through venison

consumption

Will vaccination of deer interfere with cattle testing?

• Possible cattle exposure to BCG

• False positive skin test results

• False positive IFN-gamma test results

Cattle (n=12): no conversion on skin test or Bovigam, all culture results negative

Unvaccinated sentinel deer (n=10)

BCG SC vaccinated deer (n=19)

13 vaccinated deer9 in-contact deer7 calves

27 weeks of indirect contact

No residual BCG

No evidence of transmission of BCG from Vaccinated deer to cattle

Immunological evidence of deer to deertransmission of BCG

Possums- NZBadgers- UK, Ireland

Wild boar- Spain

White-tailed deer- US

Testing a molasses-based bait for oral vaccination of white-tailed deer (Odocoileus virginianus) against Mycobacterium bovis- M. R. Stafne, BS, Iowa State University, College of Veterinary Medicine

Physical stability

BCG Survivability

Observations

Future• Bait

– Alternative Baits– Vaccine Delivery Mechanism– More field testing (attraction, stability, non-targets)

• Vaccine– Duration of immunity– Protection through secondary vaccination– Effect of high doses on protection

• Red tape– USDA, Michigan DNR, Michigan Department of Agriculture Approval

for BCG in deer– Environmental impact statement, etc.