Fig. 6.

Clearance of phage by heteropolymers (HPs) in baboons, complement receptor 1 (CR1)-transgenic and wild-type mice. (a) HP-mediated clearance of phage in baboons. Healthy baboons were injected intravenously (i.v.) with 1·5 × 10¹¹ plaque-forming units (PFU) of phage at time − 20 min. After 20 min, at time 0, the animals were injected intravenously (i.v.) with saline, 0·3 mg ΦX-CR1 HP [sulphosuccynimidyl 4-(N-maleimidomethyl (SMCC) or polyethylene glycol (PEG)] or ΦX-PA HP (SMCC). Blood was sampled 15 and 10 min pre-HP infusion and at multiple time-points (5–90 min) post-HP infusion. The graph represents the reduction in phage titre seen in blood at various times post-treatment. Due to limitations in the number of bleeds allowed, animals were not bled at time 0 immediately before HP administration. The values were normalized by subtracting the mean log₁₀ (PFU/ml) found to be present in each group at time −10 min. Because the saline group shows no change in titre over the 120 min study, we would not expect a change in titre during the 15-min interval between this point and the time of HP administration. These values were 8·27 ± 0·78, 8·75 ± 0·1, 8·63 ± 0·13 and 8·54 ± 0·23 for saline, ΦX-CR1 HP (PEG), ΦX-CR1 HP (SMCC) and ΦX-PA HP (SMCC), respectively. The plots represent the means, and the bars the range, n = 2. (b) HP-mediated clearance of phage in wild-type versus CR-1 transgenic mice. ΦX-CR1 HP (SMCC) was compared against ΦX-PA (SMCC) for its ability to clear injected bacteriophage ΦX174 from the bloodstream in CR1 transgenic and C57BL/6 wild-type mice. Phage was injected i.v. at a dose of 3 × 10⁷ PFU/mouse at time −45 min. The HPs or saline control were injected i.v. at time 0 at a dose of 1 µg/mouse. Blood was sampled at −15 min, 15 min, 90 min and 5 h post-HP injection by tail bleed. The graph represents the reduction in phage titre seen in blood at time post-treatment. The values were normalized by subtracting the mean log₁₀ (PFU/ml) found to be present in each group at time −15 min. Because the saline group shows no change in titre over the 5-h study, we would not expect a change in titre from −15 min to time 0. These −15-min values were 6·93 ± 0·30, 7·45 ± 0·08, 6·82 ± 0·32, 7·35 ± 0·11 and 6·96 ± 0·40 for saline, CR1 mouse +ΦX-CR1 HP, CR1 mouse +ΦX-PA HP, wild-type mouse +ΦX-CR1 HP and wild-type mouse +ΦX-PA HP, respectively. Error bars represent standard errors of the means, n = 3. Asterisks indicate significant difference from the ΦX-PA HP at a P < 0·05 by Student's t-test.