Figure 5.
Active immunization with Staphylococcus aureus glycoconjugate vaccines protects mice against bacteremia, weight loss, and renal abscesses. A–C, Mice immunized on days 0, 14, and 28 with CP5-Epa and challenged by the intraperitoneal route with approximately 107 colony-forming units (CFU) of S. aureus Reynolds (CP5) had fewer bacteria recovered from the blood (A; P = .0029) and kidneys (B; P < .0001) and showed reduced weight loss (C; P = .005), compared with mice immunized with Shigella O1-Epa. D, Mice immunized with 0.2 µg CP8-Epa and challenged with 3.9 × 107 CFU Reynolds (CP8) showed reduced bacteremia compared to control mice (P = .0015). E and F, Mice immunized with 0.2 µg CP5-20 µg HlaH35L were protected against bacteremia (E) and weight loss (F) provoked by challenge with approximately 107 CFU strain Reynolds (CP5). Horizontal lines represent group medians. Statistical analysis was performed with a Mann–Whitney U test (*P < .05, **P < .01, and ***P < .0001). G, Inverse correlation (P < .001 by Spearman nonparametric analysis) between mouse CP5 antibody levels and bacteremia levels in mice actively immunized with CP5-HlaH35L, 2a-Epa, or buffer. Mouse sera obtained 1 day before bacterial challenge were diluted 1:100 and tested by a CP5-specific enzyme-linked immunosorbent assay. Mice were challenged intraperitoneally with 1 × 107 CFU of S. aureus Reynolds, and quantitative blood cultures were performed after 2 hours. Each dot represents a sample from 1 mouse, and the lower limit of detection for bacteremia levels ranged from 5 to 20 CFU/mL.