Figure 1.

High dose H56 in post-exposure vaccination is detrimental to protection against Mycobacterium tuberculosis (Mtb). Total lung bacterial burden (log₁₀ CFU) for unvaccinated control (open triangle) and 5 µg H56 in CAF01 vaccinated (closed diamond) mice in preventive (A) and post-exposure (B) vaccination TB protection models. (A) CB6F1 mice were vaccinated (gray arrows) s.c. three times and rested 6 weeks before low dose aerosol Mtb challenge and subsequent lung CFU determination at weeks 3, 6, and 12 post-infection. Symbols represent mean ± SEM of n = 6–8 mice/group. ***p < 0.001, ****p < 0.0001 by two-way ANOVA with Tukey’s posttest for multiple comparisons at each time point. (B) CB6F1 mice were aerosol-infected with Mtb and treated with antibiotics (gray box; Abx) prior to three s.c. H56 vaccinations (gray arrows, weeks 10, 13, and 16) and subsequent CFU determination 37 weeks post-infection. Symbols represent mean ± SEM, n = 4–6 mice/grp (weeks 0–12) and 15/group (week 37). *p < 0.05 Mann–Whitney test at week 37. (C) Meta-analysis of Δlog₁₀ protection values (see Materials and Methods for calculation) for the indicated H56 dose using combined data from three independent preventive (open circles, 6 weeks post Mtb) and nine independent post-exposure (filled squares, 37 weeks post Mtb) vaccination experiments. Symbols, median ± 95% CI of n = 21–129 mice/group. **p < 0.01, ****p < 0.0001 by Kruskall–Wallis non-parametric test with Dunn’s test for multiple comparisons (vaccine groups vs. controls, separate analyses for preventive/post-exposure model).