Skip to main content
. 2012 Dec 14;4(12):3754–3784. doi: 10.3390/v4123754

Table 3.

Efficacy of peri-exposure treatment in animal models of Ebola virus disease.

Peri- exposure Treatment Dose and Route of Administration Mouse Model Guinea Pig Model NHP Model
Virus Vectors
VSV ∆GP Immunogens Mice: IP 2 x 105 VSV ∆GP/EBOV GP PFU -1 day before or +30 minutes or +1 day after challenge [51]

  • Complete protection with VSV ∆GP/EBOV GP regardless of time of treatment [51]

  • Mild weight loss on + 1 day, suggesting viral replication

  • 66, 83, or 50% protection with VSV ∆GP/EBOV GP -24 or +1 or 24 hours, respectively [51]

  • 50% protection with VSV ∆GP/EBOV GP +20–30 minutes [51]

  • EBOV GP [51]

Guinea pigs: IP 2 x 105 VSV ∆GP/EBOV GP PFU -24 hours or +1 or 24 hours [51]
NHPs: IM 2 x 107 PFU of VSV ∆GP/EBOV GP [51] +20–30 minutes
Passive Immunity
Pooled immune serum to live EBOV [46,52] Mice: IP 1 mL of antisera (anti-EBOV IgG titers of ≥6,400) -1 day or + 1 day [46]

  • 89% protection with pretreatment with immune serum [46]

  • Complete protection with postchallenge treatment with immune serum

  • Protection correlated with anti-EBOV IgG titers

  • No protection or delay in death with immune serum compared to controls [52]

  • Rapid decline of anti-EBOV IgG titers by day +3

  • Comparable viremia in treated and control NHPs
NHPs: IV 6 mL/kg whole blood immediately after challenge and +3 or 4 days (anti-EBOV IgG ELISA titers of 100,000) [52]
Passive Immunity
Purified polyclonal IgG antibody against:

  • Unknown, EBOV-immunized horses [53,54]

 Mice:

  • 25% protection with horse IgG at highest dose only; lower doses not effective [54]

  • Complete protection with horse IgG given at day 0 only; no viremia detected [54]

  • Complete protection with horse IgG with second dose at day +3; viremia not detected

  • No protection if IgG is delayed until day +4; transient reduction in viremia and anti-EBOV titers not detected

  • No protection with horse IgG immediately postchallenge [53,54] or -2 days [54]

  • Delayed viremia with reduction in anti-EBOV titers with NHPs receiving IgG immediately after challenge; no delay in death

  • 33% protection with 2 doses of horse IgG

  • SC 0.03, 0.3, 3 mL/kg horse IgG (log serum neutralization index of 4.2) +20–30 minutes [54]

Guinea Pigs: IM 1 mL/kg of horse IgG + several minutes and +3 days, or +4 days only [54]
NHPs:

  • IM ~1 mL/kg of horse IgG -2 days or day 0 [53,54], or day 0 and day +5 [54]

mAb EBOV GP-specific Guinea Pigs:

  • No protection when human mAb given +6 hours [55]

  • 100% protection at highest dose (50 mg/kg) when human mAb given at time of challenge or -1 hour (25 mg/kg)

  • 80% protection if human mAb given +1 hour

  • No protection with human mAb [56]

  • Minimal effect on EBOV viral replication

  • Cellular immunity may be needed for protection

  • IP 0.5, 5, 50 mg/kg +several minutes [55]

  • IP 25 mg/kg -1 hour, or +1 or 6 hours
NHPs: IV 50 mg/kg -1 day and +4 days [56]
Antiviral Agents
Antisense Phosphorodiamidate morpholino oligomers (PMO) [57,58,59,60] Mice:

  • Complete protection with highest dose of 3 PMOs each targeting VP24, VP35, or L either pre- or postexposure [58]

  • Complete protection following pretreatment with 500 µg (2 doses) of PMO targeting VP35 [57,58]

  • Complete protection following pretreatment with PMOs targeting VP24 and VP35 [58,59]

  • Postexposure protection diminishes with delay of administration of piperazine-enriched PMOs targeting VP24 and VP35 [59]

  • <75% protection with combination of PMOs each targeting VP24, VP35, or L given +6 days [58]

  • <50% protection with combination PMOs given +1 day

  • <25% protection with combination PMOs given -1 day

  • Reduction in viral titer correlated with survival

  • 50% protection with PMOs each targeting VP24, VP35, or L [58]

  • High anti-EBOV antibodies and T cell responses in survivors

  • No protection with PMO targeting VP35 only

  • 62.5% protection with SC and IP piperazine-enriched PMOs targeting VP24 and VP35 [59]

  • Dose dependent protection (0-60%) with IV piperazine-enriched PMOs targeting VP24 and VP35

  • IP 5, [58] 50, [58] or 500 [57,58] µg of PMO targeting VP35 at -1 day and -4 hours

  • IP 1, 5, or 50 [58,60] or 500 µg [60] of 3 PMOs targeting VP24, VP35, or L -4 hours or +1 day [58,60]

  • IP 10 mg/kg of PMO with piperazine moieties targeting VP24 and VP35 -1 day or +1–4 days [59]

Guinea Pigs: IP 10 mg of each PMO targeting VP24, VP35 or L -1 day or +1 or 6 days after challenge [58] Reduced viremia and release of IL-6 and MCP-1 with PMOs targeting VP24 and VP35
Antiviral Agents
Antisense PMOs (continued) s:

  • 100 times lower viral titers in treated NHPs than in NHPs receiving control PMOs targeted to MARV proteins

  • SC, IP, and IM of PMO(s) targeting VP35 or VP24, VP35, or L -2 days to through +9 days [58]

  • SC and IP of piperazine-enriched PMOs 40 mg/kg targeting VP24 and VP35 +30–60 minutes then daily for +10 or 14 days [59]

  • IV 4, 16, 28, or 40 mg/kg of piperazine-enriched PMOs targeting VP24 and VP35 +30–60 minutes then daily for +14 days

AAbbreviations: EBOV: Zaire ebolavirus species; GP: glycoprotein; Ig: immunoglobulin; IL-6: interleukin-6; IM: intramuscular; IP: intraperitoneal; IV: intravenous; L: L polymerase; mAb: monoclonal antibody; MCP-1: monocyte chemotactic protein-1; NHP: nonhuman primate; PFU: plaque-forming units; PMO: antisense phosphorodiamidate morpholino oligomers; RNA: ribonucleic acid; SC: subcutaneous; VP: viral protein; VSV: vesicular stomatitis virus