Table 2.
Antibody based therapeutics for LASV in NHP models.
| Animal Model | Challenge | Treatment Regimen | Survival | Reference |
|---|---|---|---|---|
| Immune Plasma | ||||
| Cynomolgus Macaque | SQ 1.0 × 106.1 PFU LASV Josiah | Plasma from Rhesus Macaque convalescent 180–240 days | [94] | |
| (1) 1 mL/kg LNI 4.1, IFA 1280 plasma given 0, 3, and 6 dpi IV (N = 8) | (1) 88% | |||
| (2) 1 mL/kg LNI 2.6, IFA 320 plasma given 0, 3, and 6 dpi IV (N = 3) | (2) 0% | |||
| (3) 3 mL/kg LNI 2.6, IFA 320 plasma given 0, 3, and 6 dpi IV (N = 4) | (3) 100% | |||
| (4) 3 mL/kg LNI 1.5, IFA 80 plasma given 0, 3, and 6 dpi IV (N = 3) | (4) 0% | |||
| (5) 3 mL/kg LNI 1.5, IFA 80 plasma given 0, 3, 6, 9, and 12 dpi IV (N = 3) | (5) 0% | |||
| (6) 3 mL/kg LNI 0.5, IFA 20 plasma given 0, 3, and 6 dpi IV (N = 3) | (6) 0% | |||
| (7) Untreated controls (N = 20) | (7) 5% | |||
| Cynomolgus Macaque | SQ 1.0 × 106.1 PFU LASV Josiah | Plasma from human 2–3 years convalescent | [94] | |
| (1) 3 mL/kg LNI 1.6 plasma given 0, 3, and 6 dpi IV (N = 4) | (1) 0% | |||
| (2) 12 mL/kg LNI 1.6 plasm given 0, 3, and 6 dpi IV (N = 4) | (2) 0% | |||
| (3) Control plasma (N = 4) | (3) 0% | |||
| Cynomolgus Macaque | SQ 1.0 × 106 PFU LASV Macenta | Plasma from human 2–3 years convalescent | [94] | |
| (1) 3 mL/kg LNI 2.8 plasma given 0, 3, and 6 dpi IV (N = 4) | (1) 75% | |||
| (2) 12 mL/kg LNI 2.8 plasm given 0, 3, and 6 dpi IV (N = 4) | (2) 100% | |||
| (3) Untreated controls (N = 4) | (3) 0% | |||
| Cynomolgus Macaque | SQ 1.0 × 106.1 PFU LASV Josiah | Plasma from Rhesus Macaque convalescent 180–240 days | [52] | |
| (1) 1 mL/kg 4.1 LNI plasma given 0, 3, and 6 dpi IV (N = 8) | (1) 88% | |||
| (2) 1 mL/kg 4.1 LNI plasma given 4, 7, and 10 dpi IV (N = 3) | (2) 66% | |||
| (3) 1 mL/kg 4.1 LNI plasma given 7, 10, and 13 dpi IV (N = 6) | (3) 17% | |||
| (4) Untreated controls (N = 14) | (4) 7% | |||
| HuMAb 8.9F | ||||
| Cynomolgus Macaque | IM 3500 PFU target dose LASV Josiah | (1) 15 mg/kg on 0, 4, and 8 dpi (N = 4) | (1) 100% | [95] |
| (2) Pooled controls (N = 7) | (2) 0% | |||
| HuMAb 12.1F | ||||
| Cynomolgus Macaque | IM 3500 PFU target dose LASV Josiah | (1) 15 mg/kg on 0, 4 and 8 dpi (N = 3) | (1) 100% | [95] |
| (2) Pooled controls (N = 7) | (2) 0% | |||
| HuMAb 37.7H | ||||
| Cynomolgus Macaque | IM 3500 PFU target dose LASV Josiah | (1) 15 mg/kg on 0, 4, and 8 dpi (N = 3) | (1) 100% | [95] |
| (2) Pooled controls (N = 7) | (2) 0% | |||
| HuMAb 37.2D | ||||
| Cynomolgus Macaque | IM 3500 PFU target dose LASV Josiah | (1) 15 mg/kg on 0, 4 and 8 dpi (N = 4) | (1) 100% | [95] |
| (2) 6 mg/kg on 0, 4, and 8 dpi IV (N = 2) | (2) 100% | |||
| (3) Pooled controls (N = 7) | (3) 0% | |||
| HuMAb 19.7E | ||||
| Cynomolgus Macaque | IM 3500 PFU target dose LASV Josiah | (1) 15 mg/kg on 0 and 5 dpi IV (N = 4) | (1) 75% | [95] |
| (2) Pooled controls (N = 7) | (2) 0% | |||
| HuMAb 19.7E + 37.2D | ||||
| Cynomolgus Macaque | IM 3500 PFU target dose LASV Josiah | (1) Total dose 15 mg/kg on 0, 4, and 8 dpi IV (N = 4) | (1) 100% | [95] |
| Equal mixture | ||||
| (2) Pooled controls (N = 6) | (2) 0% | |||
| HuMAb 8.9F + 12.1F + 37.2D | ||||
| Cynomolgus Macaque | IM 3500 PFU target dose LASV Josiah | (1) 15 mg/kg on 3, 6, and 9 dpi IV (N = 4) | (1) 100% | [95] |
| (2) 15 mg/kg on 6, 9, and 12 dpi IV (N = 4) | (2) 100% | |||
| (3) 15 mg/kg on 8, 11, and 14 dpi IV (N = 5) | (3) 100% | |||
| (4) Pooled controls (N = 6) | (4) 0% | |||
| 15 mg/kg of each MAb | ||||
IM = intramuscular. SQ = subcutaneous. LNI = Log10 neutralization index = (Log10 (PFU in control)-Log10 (PFU in test serum)) (LNI determined based on challenge strain) (Jahrling 1983). IFA = indirect fluorescent antibody. IP = intraperitoneal. IV = intravenous. DPI = days post infection. N = group size. PFU = plaque forming units. LASV = Lassa virus.