Table 1 Clinical findings.

From: Immune correlates of postexposure vaccine protection against Marburg virus

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

 
  1. 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).
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