Animal Models of Tuberculosis: An Overview

FIGURE 1

The theoretical relationship among virulence, immunogenicity, and fitness, and its importance in the assessment of vaccine efficacy. In assessing whether a vaccine is active, the vaccine to challenge (or boost) interval is critical. In most protocols, this interval is relatively short, and so a boosting candidate, or the challenge infection itself, is given before the effector immune response has completely contracted and the subsequent memory immune response (the true target) has become fully established. After challenge, the change in CFU levels versus time indicates the intrinsic virulence of the strain used. If the vaccine has induced memory immunity, the growth of the challenge infection is slowed, but the rapidity with which this happens also depends on the immunogenicity of the organism. Finally, recent studies (see reference 18 , for example) indicate that certain clinical strains, despite high virulence, are very effectively controlled by BCG vaccination, suggesting low fitness, whereas others are transiently inhibited but after a while continue to grow progressively.