Table 1.
Clinical findings.
| Animal # Weight Sex | Clinical Observations | GP-specific IgM | GP-specific IgG | Final Outcome | Reference |
|---|---|---|---|---|---|
| Untreated Control 1* 5.04 kg Female | Fever (6), depression (6–8), anorexia (7,8), lymphopenia (3,6), ALT +++ (6), AST +++ (6) > (8), ALP + (6), GGT + (6), CRP increase (3,6), tPA +++ (6), PAI-1 +++ (6) | None | None | Succumbed 8 DPI | 17 |
| Untreated Control 2* 4.04 kg Female | Fever (6), depression (8,9), anorexia (7–9), mild to moderate petechial rash (8,9), BUN ++ (9), CRE + (9), ALT ++ (6) +++ (9), AST +++ (6,9), ALP ++ (9), GGT +++ (9), CRP increase (9), p-selectin +++ (9), d-dimer + (9), tPA + (6) +++ (9), PAI-1 + (6) +++ (9), factor IX + (3) | None | None | Succumbed 9 DPI | 17 |
| Untreated Control 3* 4.54 kg Female | Fever (6), depression (10), anorexia (8,10), mild to moderate petechial rash (10), emesis (8), leukocytosis (6,10), granulocytosis (3,6), CRE + (10), ALT +++ (10), AST + (6) +++ (10), ALP +++ (10), GGT +++ (10), CRP increase (6,10), d-dimer ++ (6), tPA + (3) ++ (6), PAI-1 ++ (6,10) | None | None | Succumbed 10 DPI | 17 |
| Vector Control* 4.76 kg Male | Depression (12), anorexia (10–12), mild petechial rash (10–12), BUN + (12), CRE ++ (12), ALT +++ (10,12), AST +++ (10,12), ALP ++ (10,12), GGT +++ (10,12), CRP increase (10,12), d-dimer +++ (3,6,10,12), tPA ++ (10) +++ (12), sCD40L + (10), PAI-1 + (10) +++ (12), factor IX ++ (3) | None | None | Succumbed 12 DPI | 17 |
| ∆G Treated Fatal* 5.56 kg Female | Fever (6), depression (10,11), anorexia (8,9,11), mild to moderate petechial rash (10), ecchymotic rash (11), leukocytosis (11), lymphopenia (6,10), granulocytosis (3,6,10,11), thrombocytopenia (10), BUN + 10) +++ (11), CRE +++ (11), ALT > (10,11), AST > (10,11), ALP ++ (10,11), GGT +++ (10,11), CRP increase (6,10,11), p-selectin + (6) ++ (3) +++ (10,11), d-dimer + (11), PSGL-1 + (3,10), tPA ++ (10) +++ (11), PAI- 1 +++ (10,11), factor IX ++ (10) | None | None | Succumbed 11 DPI | 17 |
| ∆G Survivor 1* 3.64 kg Male | Granulocytosis (21), p-selectin + (3,10) ++ (6), PSGL-1 + (3,6,14,21,28), factor IX + (14) | 100 (10), 200 (14), 100 (21), 100 (28) | 800 (10), 3,200 (14), 3,200 (21), 6,400 (28) | Survived | 17 |
| ∆G Survivor 2* 3.70 kg Male | CRP increase (28), p-selectin + (14) ++ (28), PSGL-1 + (6) ++ (21,28) | 200 (10), 200 (14), 100 (21), 100 (28) | 800 (10), 800 (14), 1600 (21), 6400 (28) | Survived | 17 |
| ∆G Survivor 3* 4.80 kg Female | PSGL-1 + (6,10), factor IX + (6,14,21,28) ++ (10) | 100 (10), 100 (14), 100 (21) | 800 (10), 1,600 (14), 3,200 (21), 6,400 (28) | Survived | 17 |
| ∆G Survivor 4 4.06 kg Female | None | 100 (10), 100 (14) | 3,200 (10), 3,200 (10), 6,400 (21), 6,400 (28) | Survived | |
| ∆G Survivor 5 4.30 kg Female | Fever (6), mild depression (8,9), mild to moderate petechial rash (8,9,10,11), lymphopenia (6), ALT + (21) +++ (10,14), AST + (14) +++ (10), ALP ++ (10), GGT + (14,21) +++ (10), CRP increase (10), tPA ++ (10), PAI-1 ++ (14) +++ (10), factor IX + (3) ++ (21) +++ (6,10,14) | 1600 (10), 800 (14), 200 (21), 100 (28) | 100 (6), 1,600 (10), 3,200 (14), 6,400 (21), 12,800 (28) | Survived | |
| ∆G Survivor 6 4.06 kg Female | Thrombocytopenia (28), p-selectin + (3) ++ (28), tPA + (28), PAI-1 +++ (28) | 100 (10), 200 (14), 100 (21) | 400 (10), 1,600 (14), 1,600 (21), 6,400 (28) | Survived | |
| ∆G Survivor 7 4.60 kg Female | Granulocytosis (6), factor IX + (3,14) | 100 (10), 100 (14) | 100 (6), 1,600 (10), 1,600 (14), 3,200 (21), 3,200 (28) | Survived | |
| ∆G Survivor 8 4.36 kg Female | d-dimer ++ (28), sCD40L ++ (10,14,21) +++ (3,6,28), factor IX + (3,6,21,28) | 100 (10), 100 (14) | 100 (6), 1,600 (10), 1,600 (14), 1,600 (21), 3,200 (28) | Survived | |
| N2 Treated Fatal 5.10 kg Male | Depression (12,13,14), anorexia (12), mild to moderate petechial rash (13,14), mild dyspnea (14), lymphopenia (10), granulocytosis (10,14), thrombocytopenia (10,14), BUN ++ (14), CRE + (14), ALT + (10) +++ (14), AST ++ (10) +++ (14), ALP ++ (14), GGT + (14), CRP increase (10,14), p-selectin + (6), d-dimer + (6,10,14), tPA +++ (14), PAI-1 + (3) ++ (10) +++ (14), factor IX + (14) | None | 200 (14) | Succumbed 14 DPI | |
| N2 Survivor 1 4.28 kg Male | Fever (6), CRP increase (6) | 100 (6), 400 (10), 400 (14), 200 (21), 100 (28) | 1,600 (10), 3,200 (14), 3,200 (21), 3,200 (28) | Survived | |
| N2 Survivor 2 4.94 kg Female | ALT + (6,10,14) | 100 (6), 100 (10), 100 (14) | 800 (10), 800 (14), 1,600 (21), 1,600 (28) | Survived | |
| N2 Survivor 3 4.78 kg Female | P-selectin +++ (10,14), d-dimer + (10,14), tPA +++ (10,14), PAI-1 +++ (10,14) | 100 (6), 100 (10), 100 (14) | 100 (6), 3,200 (10), 3,200 (14), 6,400 (21), 6,400 (28) | Survived | |
| N2 Survivor 4 4.22 kg Female | ALT ++ (10), d-dimer + (3,6,14,21,28), PSGL-1 + (3), tPA + (3,14), sCD40L + (14) ++ (3,28), PAI-1 + (3), factor IX + (10) ++ (3,14,28) | 200 (10) | 800 (10), 1,600 (14), 1,600 (21), 3,200 (28) | Survived |
Animals were monitored daily for clinical signs. Hematological changes, serum biochemistry values, and reciprocal dilution anti-MARV-GP IgM and IgG titers were evaluated in NHP subjects at 0, 3, 6, 10, 14, 21, and terminally, or at 28 days after challenge. The DPI for each parameter is indicated in parentheses. An asterisk (*) denotes a historical sample. Fever: temperature greater than 3.0 °F above baseline or at least 1.5 °F above baseline and ≥104.0 °F. Lymphopenia and thrombocytopenia: ≥35% drop in numbers of lymphocytes, and platelets respectively. Leukocytosis and granulocytosis: ≥ two-fold increase in leukocytes and granulocytes respectively. Crosses indicate increases in liver enzymes (ALT, AST, ALP, GGT), renal function test values (BUN, CRE), or coagulation-associated analytes (p-selectin, d-dimer, PSGL-1, tPA, sCD40L, PAI-1, factor IX): 2- to 3-fold increase, +; >3- up to 5-fold increase, ++; >5 fold increase, +++; out of range, >. CRP increase refers to samples with concentrations >10 mg/L. Abbreviations: ∆G (referring to individual monkey treated with rVSV∆G/MARV-Angola-GP); N2 (referring to individual monkey treated with rVSVN2CT1-MARV-Angola GP); BUN (blood urea nitrogen); CRE (creatinine); ALT (alanine aminotransferase); AST (aspartate aminotransferase); ALP (alkaline phosphatase); GGT (gamma-glutamyltransferase); CRP (c-reactive protein); PSGL-1 (p-selectin glycoprotein ligand-1); tPA (tissue plasminogen activator); sCD40L (soluble CD40-ligand); PAI-1 (plasminogen activator inhibitor-1); IgM (immunoglobulin M); IgG (immunoglobulin G); DPI (days post-infection).