Setting: The Australian brushtail possum is the major wildlife reservoir for Mycobacterium bovis infection in New Zealand. Development of an effective tuberculosis vaccine for possums will reduce the spread of infection to cattle and farmed deer.

Objectives: To determine whether killed M. vaccae can improve the efficacy of vaccination with M. bovis bacillus Calmette Guerin (BCG) against bovine tuberculosis in the possum.

Design: Groups of possums (n=6–8) were vaccinated via intranasal and intraconjunctival routes with BCG alone or BCG in combination with heat-killed M. vaccae. Controls were non-vaccinated or vaccinated with heat-killed M. vaccae alone. After challenge with virulent M. bovis, protection was assessed by a reduction in loss of body weight and bacterial counts in lungs and spleens. Blood lymphocyte proliferative responses to M. bovis purified protein derivative were monitored throughout.

Results: The earliest lymphocyte responses following vaccination were from animals inoculated with BCG plus 100 μg heat-killed M. vaccae. Loss of body weight was significantly reduced in all BCG-vaccinated groups compared control groups. Spleen bacterial counts were significantly lower in animals vaccinated with M. vaccae plus BCG compared to the non-vaccinated group. Furthermore, vaccination with 100 μgM. vaccae plus BCG significantly reduced spleen bacterial counts compared to vaccination with BCG alone.

Conclusion: The possum infection model is one of the first to show that novel vaccine strategies may offer better protection against tuberculosis than BCG alone.