Table 1.
Cohort descriptions for three studies to assess efficacy of tip and tail derived polyclonal and monoclonal antibodies.
| Study | Host (n) | Treatment | Dose |
|---|---|---|---|
| Resolution of experimental NTHI-induced OM via treatment with polyclonal or monoclonal antibodies | Chinchilla (6) | Naive rabbit serum | 5.0 μg |
| Chinchilla (6) | Rabbit anti-IHFE. coli | 5.0 μg | |
| Chinchilla (6) | Rabbit anti-IHFNTHI | 5.0 μg | |
| Chinchilla (6) | Rabbit anti-HUNTHI | 5.0 μg | |
| Chinchilla (6) | MAb IhfA3NTHI | 5.0 μg | |
| Chinchilla (6) | MAb IhfA5NTHI | 5.0 μg | |
| Chinchilla (6) | MAb IhfB2NTHI | 5.0 μg | |
| Chinchilla (6) | MAb mIhfB4NTHI | 5.0 μg | |
| Chinchilla (6) | MAb IhfA3NTHI + IhfB2NTHI | 5.0 μg each | |
| Chinchilla (6) | MAbs IhfA3NTHI + IhfB2NTHI | 2.5 μg each | |
| Chinchilla (6) | MAbs IhfA5NTHI + mIhfB4NTHI | 5.0 μg each | |
| Chinchilla (6) | MAbs IhfA5NTHI + mIhfB4NTHI | 2.5 μg each | |
| Clearance of P. aeruginosa from the murine lung via delivery of MAb cocktails | Mouse (5) | None | None |
| Mouse (10) | Murine IgG1 | 10.0 μg antibody | |
| Mouse (10) | MAbs IhfA3NTHI + IhfB2NTHI | 5.0 μg each antibody | |
| Mouse (10) | MAbs IhfA3NTHI + IhfB2NTHI | 5.0 μg each antibody | |
| Clearance of P. aeruginosa from the murine lung via delivery of MAb cocktails ± tobramycin | Mouse (5) | None (sacrificed prior to treatment) | None |
| Mouse (3) | None | None | |
| Mouse (10) | Murine IgG1 + IgG2a | 5.0 μg each antibody | |
| Mouse (13) | Murine IgG1 + IgG2a + tobramycin | 5.0 μg each antibody + 60 mg tobramycin/kg | |
| Mouse (10) | MAbs IhfA3NTHI + IhfB2NTHI | 5.0 μg each antibody | |
| Mouse (13) | MAbs IhfA3NTHI + IhfB2NTHI + tobramycin | 5.0 μg each antibody + 60 mg tobramycin/kg | |
| Mouse (10) | MAbs IhfA5NTHI + mIhfB4NTHI | 5.0 μg each antibody | |
| Mouse (13) | MAbs IhfA5NTHI + mIhfB4NTHI + tobramycin | 5.0 μg each antibody + 60 mg tobramycin/kg | |
| Mouse (10) | Tobramycin | 60 mg tobramycin/kg |
In vitro, 5 μg MAb is typically added to each well of a chamberside to disrupt a 24 h biofilm which contains approx. 8 × 107 CFU NTHI per well of a chamberslide (includes both planktonic and biofilm-resident bacteria) (Brockson et al., 2014). In vivo, 4 days after TB challenge of a naive chinchilla there are approx. 108 CFU NTHI/ml MEF and ~ 106 CFU NTHI/mg mucosal biofilms (total of ~ 108 CFU/ml in the middle ear space) (Novotny et al., 2015a). Similarly, mice were challenged with 107 CFU of P. aeruginosa the day before administration of MAbs. Thereby, as a first approximation, we used what was known to be an effective dose in vitro to disrupt a biofilm that contained the approximate number of bacteria we expected to be within either the middle ear of chinchillas or lungs of mice and used this dose in our animal model systems.