Figure 8. Extension of the therapeutic window of the live attenuated SterneΔhtrA spore vaccine compared to the Sterne parental vaccine strain in guinea pigs.

This figure is based on results summarized in Table 2, Figs 4, 5, and 6 and on the Sterne vaccinated guinea pig protection data; a, upper panel: Sterne strain; lower panel: SterneΔhtrA strain. The red line (black triangles) represents the survival profile of guinea pigs immunized with increasing doses of spores as indicated on the left y-axis (red text). The blue dotted line represents the survival after challenge of the guinea pigs immunized with the indicated single or double spore doses. Note: (i) Not all the animals immunized with Sterne spores at doses lower than the LD₅₀ survived the lethal challenge of Vollum, and 50% survival after such a challenge (Protective Dose 50%, PD₅₀) is achieved by administration of a Sterne dose close to the LD₅₀ value of the strain. (ii) Unlike the Sterne vaccine, 100% survival can be achieved with the SterneΔhtrA vaccine strain at a vaccination dose much lower than the LD₅₀ value of the Sterne ΔhtrA vaccine. Panel b: The calculated “therapeutic window” was determined from the ratio between the safety (LD₅₀) and the efficacy (PD₅₀) values of the two vaccine strains. Note that for SterneΔhtrA, only a lower limit of the LD₅₀ was determined (Fig. 3 and Table 2), and therefore, the therapeutic window may be even wider than has been estimated in this figure.