Figure 4. pIgR-binding Cam-003 fusions elicit opsonophagocytic killing and improved protection against lethal challenge in a P. aeruginosa acute pneumonia model.

(A) Opsonophagocytosis assay with luminescent P. aeruginosa serogroup 05 strain PAO1 (PAO1.lux). OPK with Cam-003–QRN, Cam-003–KLKL, and Cam-003 are shown with the isotype control IgG R347. (B–D) Survival of BALB/c mice prophylactically immunized with an IgG isotype control R347, Cam-003, and either Cam-003–QRN (B) or Cam-003–KLKL (C and D) prior to i.n. infection with P. aeruginosa strain 6077. Results are represented as Kaplan-Meier survival curves; differences in survival were calculated by the log-rank test (Mantel-Cox). Data are representative of at least 2 independent experiments; n = 10 per group for survival experiments. (B) Cam-003 and Cam-003–QRN had significantly better protection than the isotype control at both doses tested (P < 0.0001 for both 5 and 10 mg/kg doses; 4.5 × 10⁵ CFU inculcation). Cam-003–QRN survival was significantly improved compared with Cam-003, as well (P = 0.0014 for 5 mg/kg doses and P = 0.0098 for 10 mg/kg doses). (C) At 5 × 10⁵ CFU, Both Cam-003 and Cam-003–KLKL were protective compared with R347 at both doses (P = 0.017, 2 mg/kg Cam-003; P = 0.0004, 6 mg/kg Cam-003; P < 0.0001, 2 and 6 mg/kg doses of Cam-003–KLKL). Cam-003–KLKL survival was superior to Cam-003 when comparing both the 2 mg/kg doses (P = 0.0042) and 6 mg/kg doses (P = 0.017). (D) At an 8 × 10⁵ CFU inoculum dose, Cam-003 and Cam-003–KLKL survival was again enhanced compared with R347 (P < 0.0001, 2 mg/kg Cam-003; P = 0.0002, 6 mg/kg Cam-003; P < 0.0001, Cam-003–KLKL), with Cam-003–KLKL survival also enhanced compared with Cam-003 (P = 0.017, 6 mg/kg; not significant, 2 mg/kg).