ABSTRACT
A
Mycobacterium ulcerans
human challenge model has the potential to fundamentally advance our understanding of early human immune responses to infection, while rapidly evaluating vaccines and other therapeutic interventions. Here, using a murine tail infection model, we tested a very well-characterized working cell bank of the proposed challenge isolate
M. ulcerans
JKD8049 in naïve and
Mycobacterium bovis
bacille Calmette–Guérin (BCG)-vaccinated BALB/c mice. All 10 naïve mice were successfully infected with 20 colony-forming units (CFU) of
M. ulcerans
[95% confidence interval (CI) 17–22 CFU] with a mean time to visible lesion of 86 days (95% CI 79–92 days). In the 10 vaccinated mice, there was a significant delay in the mean time to lesion compared to the naïve controls of 24 days (
P
= 0.0003), but all mice eventually developed ulcerative lesions. This study informs a future human infection model by demonstrating the successful application of the challenge agent in this
in vivo
model and highlights both the promise and the problems with trying to induce protective immunity against
M. ulcerans
.
IMPORTANCE
In preparation for its proposed use in a controlled human infection model (CHIM), this study reports the successful infection of BALB/c mice using a carefully characterized, low-dose inoculum of
Mycobacterium ulcerans
JKD8049 (our proposed CHIM strain). We also demonstrate that
Mycobacterium bovis
bacille Calmette–Guérin delays the onset of disease but cannot alter the course of illness once a lesion becomes apparent. We also validate the findings of previous low-dose challenges that used less accurate methods to determine the inoculum, but our presented methodology is practical, accurate, and anticipated to be reproducible.
