Extended Data Fig. 11: Evaluation of the in vivo therapeutic and combined efficacy of 08O09, 05D08 and 05N02 mAbs in immunocompetent ST147NDM-1 bacteremia model, related to Fig. 5.
From: Monoclonal antibodies protect against pandrug-resistant Klebsiella pneumoniae
(A) Spleen load of ST147NDM1 c.i.1 one hour after the injection of 1.6 × 106 CFU formulated in hog gastric mucin (n = 18 animals examined in 3 independent experiments). (B) Survival analysis of 08O09 treatment (TX) regimens versus sham controls (n = 10 mice per group in 1 experiment; i.p. challenge with 1.6 × 106 CFU ST147NDM-1 c.i.1 formulated in hog gastric mucin). Kaplan-Meier survival analysis and the log rank (Mantel-Cox) test to compare each 08O09-treated group versus the respective control group resulted in the following P values: 0.0002 for 1 mg/kg; 0.0005 for 5 mg/kg, and <0.0001 for 10 and 20 mg/kg. (C) Spleen load of ST147NDM-1 in 08O09 TX study. Log10 CFU/spleen at endpoint (n = 10 animals per group in 1 experiment) was normalized to non-infected controls (n = 6 animals in 1 experiment). Two-tailed Mann-Whitney test, * p = 0.0241, **** p < 0.0001. (D) Survival analysis of 08O09 PPX, TX and PPX + TX regimens at 1 mg/kg doses (n = 10 mice per group in 1 experiment). Indicated P values were calculated by log-rank (Mantel-Cox) test and refer to a comparison of PPX + TX group versus either PPX (* p = 0.0378) or TX group (*** p = 0.0008). (E) Survival analysis of 08O09 PPX regimen at 5 mg/kg versus sham controls (n = 12 mice per group, 4 mice were monitored for 96 h and 8 mice were monitored for 192 h over 2 independent experiments; i.p. challenge with 107 CFU ST147NDM-1 c.i.1 formulated PBS). Kaplan-Meier survival analysis and the log rank (Mantel-Cox) test to compare the groups resulted in a P value of 0.0018. (F) Spleen load of ST147NDM1 c.i.1 in 08O09 PPX study (i.p. challenge with 107 CFU ST147NDM-1 c.i.1 formulated PBS). Log10 CFU/spleen at endpoint for PPX group (n = 8 animals examined over 2 independent experiments) and non-infected controls (n = 7 animals examined over 2 independent experiments). Two-tailed Mann-Whitney test, * p = 0.036.
