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

Table 2.

Efficacy of vaccines in animal models of Ebola virus disease.

Vaccines Immunization Schedule Mouse Model Guinea Pig Model NHP Model
Virus Vectors
HPIV3 Immunogens Guinea Pigs:
  • Complete protection with HPIV3/EBOV GP or HPIV/EBOV NP [29,31]

  • Strong humoral response

  • Complete protection with 2 doses of HPIV3/EBOV GP [30]

  • No advantage to bivalent vaccines

  • EBOV GP [29,30,31]

  • EBOV NP [31]

  • EBOV GP + NP [30]

  • IN 4 × 106 PFU of HPIV3/EBOV GP [29]

  • IN 105.3 PFU of HPIV/EBOV GP or NP [31]

HPIV3- NHPs:
  • IN plus IT 4 × 106 TCID50 of HPIV3/EBOV GP, HPIV3/EBOVGP+NP or 2 × 107 TCID50 of HPIV3/EBOV GP-1–2 doses [30]

VSV ∆GP Immunogens Immunocompetent Mice:
  • Complete protection in NOD-SCID mice with high-dose VSV∆GP/EBOV GP [35]

  • Complete protection with VSV∆G/EBOV GP live vector in immuncompetent mice [32,33,35] regardless of route of administration [35]

  • Complete protection with VSV∆G/EBOV GP given 7 days prior to challenge

  • Complete protection with VSV ∆GP/EBOV GP [32]

  • 67% protection with VSV ∆GP/EBOV GP in HIV+ NHPs mediated by CD4+ cells [34]

  • Complete protection with VSV ∆GP/EBOV GP [36,37,38] in immunocompetent NHPs regardless of route of vaccination

EBOV GP attenuated [32,33,34,35,36,37,38]
  • IP, IM, IN, PO 1–2 × 104 PFU of VSV∆GP/EBOV GP [32,33,35]

  • IP 2–2 × 103 PFU [35]

NOD-SCID Mice: IP 2 × 105 PFU of VSV∆GP/EBOV GP
Guinea Pigs: IP 2 × 105 PFU-1–2 doses of VSV∆GP/EBOV GP [32]
HIV + NHPs: IM 1 × 107 PFU [34]
Immunocompetent NHPs:
  • IM 1 × 107 PFU of VSV∆GP/EBOV GP [38]

  • PO, [36] IN, [36] IM [36,37] 2 × 107 PFU of VSV∆GP/EBOV GP

VV Immunogens Guinea Pigs: SC 107 of VV/EBOV GP–3 doses [39]
  • 60% protection with VV/EBOV GP [39]

  • Survival correlated with neutralizing antibodies

  • No protection with VV/ EBOV GP [24]

  • Viremia present in all subjects

NHPs: SC of VV/EBOV GP–3 doses [24]
Virus-like Particles (VLPs)
VEEV RNA (VRP) encoding: Mice:
  • 75–100% protection with VRP/EBOV NP [40,41,42]

  • 90–100% protection with VRP/EBOV GP [41,42,43]

  • Complete protection with VRP/EBOV GP+NP [41]

  • 95–100% protection with VRP/EBOV VP proteins in BALB/c mice [42]

  • 100% protection with VRP/EBOV VP 30 or VP 35 proteins in C57BL/6 mice [42]

  • 80% protection with VRP/EBOV VP40 in C57BL/6 mice [42]

  • No protection with VRP/EBOV VP24 protein in C57BL/6 mice [42,45]

  • Strain 2 guinea pigs (2 doses): no protection with VRP/EBOV NP; 60% protection with VRP-EBOV GP [41]

  • Strain 13 guinea pigs (3 doses): complete protection with VRP-EBOV GP; 20% protection with VRP/EBOV NP

  • 100% protection with VRP/EBOV GP [44]

  • No protection with VRP/EBOV GP or NP or both immunogens [24]

  • Viremia present in all subjects

  • Time to death similar to controls

  • SC 2 x 106 FFU of VRP/EBOV NP– 3 doses [40]

  • SC 2 × 106 FFU or 2 × 106 IU of VRP/EBOV NP, VP24, VP30, VP35, or VP40 for 2–3 doses [42,45]

  • SC 1 × 106IU of VRP/EBOV GP or NP or GP + NP–2 doses [41]

  • SC 1 × 108 of VRP EBOV GP–4 doses [43]

Guinea Pigs: SC 107 IU of VRP EBOV GP, NP, or GP+NP–2 or 3 doses [41,44]
NHPs: SC 2 x 106 FFU of VRP EBOV GP, NP or GP+NP–3 doses [24]
Ebola Virus Vaccines
EBOV Mice
  • Complete protection with SC, IM live EBOV; [20,22,46] protection dependent on CD8+ cells and interferon-α/β receptors and not on B or CD4+ cells [20,47]

  • Persistent infection in CD4-depleted or B cell-deficient mice [47]

  • Complete protection with IV irradiated liposome encapsulated EBOV [49]

  • 77% protection with IM liposome encapsulated EBOV

  • 25, 45, or 55% protection with IP-, IM-, or IV-irradiated EBOV, respectively [48,49]

  • >80% protection with INA-inactivated EBOV [50]

  • No protection with liposome encapsulated EBOV; viremia [49]

  • 25% protection with irradiated EBOV; viremia present in all macaques [24]

  • Neutralizing antibody titers present in 1 surviving macaque immunized with irradiated EBOV

  • Live [20,22,46,47]

  • irradiated [24,48,49]

  • irradiated, in liposomes [24,49]

  • INA+ UV irradiated, MA [50]

  • SC, IM, ID 100 PFU MA-EBOV prior to IP challenge [20,22,46,47]

  • IP 10 µg of irradiated EBOV–3 doses [48]

  • IM, IV 1.4 µg of irradiated EBOV alone or in liposome–2 doses [49]

  • IM 5 × 104 PFU of INA inactivated MA-EBOV–1 or 2 doses [50]

NHPs:
  • IV 194 µg of EBOV encapsulated in liposome–3 doses [49]

  • SC 50 µg of irradiated EBOV–3 doses [24]

Abbreviations: EBOV: Zaire ebolavirus species; FFU: focus-forming units; GP: glycoprotein; HIV: human immunodeficiency virus; GPA: guinea pig adapted; HPIV3: human parainfluenza virus type 3; IM: intramuscular; IN: intranasal; INA: 1,5-iodonaphthylazide; IP: intraperitoneal; IT: intratracheal; IV: intravenous; MA: mouse adapted; NHP: nonhuman primate; NOD: nonobese diabetic; NP: nucleoprotein; PFU: plaque-forming units; PO: oral; RNA: ribonucleic acid; SC: subcutaneous; SCID: severe combined immunodeficiency; TCID: tissue culture infective dose; VEEV: Venezuelan equine encephalitis virus; VLP: virus-like particles; VP: viral protein; VRPs: VEEV RNA replicon particles; VSV: vesicular stomatitis virus: VV: vaccinia virus