Figure 7. Immunization with P. aeruginosa D-Glu auxotroph (α-Pa vaccine) provides effective protection against diverse bacteria.
(a) Protective effect against bacterial dissemination after acute infection. Bacterial loads in tissues from vaccinated (2 × 107 CFU of α-Pa strain) and control mice after challenge with P. aeruginosa PAO1 (2 × 107 CFU) (n=8; after 10 h). *P<0.05 (Mann–Whitney U-test). (b) Early vaccine protection against infection. Mice survival after vaccination with α-Pa strain (2 × 106 and 2 × 107 CFU), or saline administration and challenge with PAO1 on day 25 (2 × 107 CFU, n=8 for BALB/c), on day 28 (4 × 107 CFU, n=4 for C57BL/6 mice) and PA28562 (4 × 107 CFU) on day 25 (n=8). (c) Different routes of immunization and vaccine protection. Mice survival after IM vaccination with α-Pa strain (2 × 107 CFU) or saline administration and challenge with PAO1 (6 × 107 CFU, n=8 for BALB/c and 2 × 107 CFU, n=8 for C57BL/6) and PA14 (4 × 106 CFU) (n=7–8). Mice survival after intranasal (IN) vaccination with α-Pa strain (2 × 107 CFU) or saline administration and challenge with PAO1 (5 × 106 CFU) (n=9). (d) Long-term vaccine protection against infection. Mice survival after vaccination with α-Pa strain (2 × 107 CFU) or saline administration and challenge with PAO1 (2 × 107 CFU) on day 98 (n=9–10) and PA14 on day 98 (4 × 106 CFU) (n=10). (e) Superior vaccine protection conferred by P. aeruginosa D-Glu auxotroph. Mice survival after vaccination with α-Pa strain (2 × 107 CFU), formalin-inactivated PAO1 (2 × 107 CFU) or saline administration and challenge with PA14 (8 × 106 CFU) (n=9). Mice survival after vaccination with α-Pa strain (2 × 107 CFU), formalin-inactivated PAO1 (2 × 107 CFU), heat-killed PAO1 (2 × 107 CFU) or saline administration and challenge with PAO1 (4 × 107 CFU) (n=8). (a–e) S, saline; I, administered the formalin-inactivated vaccine; H–K, administered the heat-killed vaccine; V, vaccinated. (b–e) *P<0.05 (log-rank test), compared with saline group. (e) #P<0.05 (log-rank test), compared with mice administered the formalin-inactivated vaccine. &P<0.05, compared with mice administered the heat-killed vaccine.