Supplemental Table 1. Efficacy of vaccines in animal models of Ebolavirus disease. Vaccines Immunization Schedule Mouse Model Guinea Pig Model NHP Model Virus Vectors HPIV3 Immunogens Guinea Pigs: Complete protection Complete protection HPIV3 ∆HN-F/ EBOV GP IN 4 x 106 PFU of HPIV3 with HPIV3 ∆HN-F/EBOV with 2 doses of [1] ∆HN-F/EBOV GP or GP, HPIV3/EBOV GP, or HPIV3/EBOV GP [3] EBOV GP [1-3] HPIV3/EBOV GP [1] HPIV3/EBOV NP [1, 2] No advantage to EBOV NP [2] IN 105.3 PFU of HPIV/EBOV Strong humoral response bivalent vaccines EBOV GP + NP [3] GP or NP [2] EBOV GP +GM-CSF [3] HPIV3- NHPs: 6 IN plus IT 4 x 10 TCID50 of HPIV3/EBOV GP, HPIV3/EBOV GP+GM-CSF, HPIV3/EBOVGP NP or 2 x 7 10 TCID50 of HPIV3/EBOV GP for 1–2 doses [3] RABV ∆GP/EBOV GP Mice: IM 5 x 105 FFU Complete protection with (Live attenuated) [4] either vector RABV/EBOV GP fused to EBOV GP incorporation into GCD of RABV virions not dependent on (inactivated) [4] RABV GCD Human Ad5 Immunogens Mice: With induced preexisting Ad5 With systemically CMVEBOV GP [5-9] IN, PO, IM 1 x 1010 [6] to 5 immunity, complete induced preexisting Ad5 CAGoptEBOV GP [8, 9] x 1010 [5] particles of protection with only IN immunity, complete Ad5/CMVEBOV GP Ad5/CMVEBOV GP [5] protection with IN IP 1 x 108 PFU With no Ad5 immunity: Ad5/CMVEBOV GP [8] Ad5/CMVEBOV GP[7] complete protection With mucosally induced IM 1 x 104–1 x 107 IFU of regardless of route [5-7, 9] preexisting Ad5 Ad5/CMVEBOV GP or 1 x Mucosal immunization Ad5- immunity, 83% 104–1 x 106 IFU of EBOV GP increased cellular protection with IN Ad5/CAGopt EBOV GP [9] and humoral immunity Ad5/CMVEBOV GP Guinea Pigs: compared to IM With systemically IN, IM 1 x 1010 particles of immunization[6] induced preexisting Ad5 Vaccines Immunization Schedule Mouse Model Guinea Pig Model NHP Model Ad5/CMVEBOV GP or Complete protection with immunity, 78% or 100% Ad5/CAGopt EBOV GP[8] Ad5/CAGopt EBOV GP and 2 protection with IM or IN higher doses of CAGopt EBOV GP, Ad5/CMVEBOV GP [9] respectively Increased cellular and With no Ad5 induced humoral responses with immunity, complete Ad5/CAGoptEBOV GP protection regardless of route AdC7/CMVEBOV GP[10] Mice: IM 5 x 109–5 x 1010 Complete protection; not Complete protection particles of AdC7/EBOV GP affected by induced Effect of preexisting Ad5 Guinea Pigs: IM 5 x 109–5 x preexisting Ad5 immunity immunity not studied 1011 particles/kg AdC5/1-CMVEBOV GP [11] Mice: IM 5 x 1010 particles Complete protection VSV ∆GP Immunogens Immunocompetent Mice: Complete protection with Complete protection 67% protection with EBOV GP attenuated IP, IM, IN, PO 1–2 x 104 VSV∆G/EBOV GP live vector with homologous VSV VSV ∆GP/EBOV GP in [12-18] or irradiated[13] PFU of VSVΔG/EBOV GP, in immunocompetent mice ∆GP/EBOV GP only [12] HIV+ NHPs mediated TAFV GP [12] TAFV GP, RESTV GP, or [12, 13, 15]regardless of 83% cross EBOV species by CD4+ cells [14] RESTV GP SUDV GP [12, 13, 15] route of administration [15] protection with 2 doses Complete protection SUDV GP IP 2–2 x 103 PFU of Complete protection with of VSV ∆GP/SUDV with homologous SUDV GP+VP40 VSVΔG/EBOV GP [15] VSV∆G/EBOV GP given 7 GP+VP40 PO,[16] IN, [16]OR IM 5 SUDV GP + NP NOD-SCID Mice: IP 2 x 10 days prior to challenge IgG antibodies against [16, 17] VSV SUDV GP+NP and SUDV PFU of VSVΔG/EBOV GP No protection with irradiated both SUDV antigens not ∆GP/EBOV GP to IM 5 GP+VP40 Guinea Pigs: IP 2 x 10 PFU vaccine [13] increased after EBOV [16, 18] or aerosol [17] of VSVΔG/EBOV GP, TAFV Complete cross-EBOV species challenge indicating lack EBOV challenge GP, RESTV GP, SUDV GP, protection with of viral replication 25% protection with SUDV GP+VP40, SUDV VSV∆GP/RESTV GP or No EBOV neutralization VSV ∆GP/EBOV GP GP+NP, SUDV GP+NP and VSV∆GP/TAFV GP [12] antibodies detected following rechallenge SUDV GP+VP40 for 1–2 75% cross-EBOV species following SUDV with SUDV [18] doses [12] protection with VSV∆G/SUDV vaccination and EBOV 7 HIV+ NHPs: IM 1 x 10 PFU of GP [12] challenge VSVΔG/EBOV GP [14] Complete protection in NOD- Reduced cross-EBOV Immunocompetent NHPs: SCID mice with high-dose species protection with 7 IM 1 x 10 PFU of VSV∆GP/EBOV GP [15] SUDV NP inclusion Vaccines Immunization Schedule Mouse Model Guinea Pig Model NHP Model VSV∆GP/EBOV GP then EBOV challenge and SUDV rechallenge [18] PO,[16] IN,[16] IM[16, 17] 2 x 107 PFU of VSV∆GP/EBOV GP 5 CMV ∆m157/EBOV NPCTL[19] Mice:IP 5 x 10 PFU–2 doses Complete protection VV Immunogens Guinea Pigs: SC 107 of 60% protection with No protection with EBOV NP[20] VV/EBOV NP, VP35, VP40, VV/EBOV GP only [20] VV/EBOV GP [21] EBOV VP35 GP, OR sGP–3 doses[20] Survival correlated with Viremia present in all EBOV VP40 NHPs: SC of VV/EBOV GP–3 development of subjects EBOV GP [20, 21] doses[21] neutralizing antibodies Time to death similar EBOV sGP [20] to controls Virus-like Particles (VLPs) VEEV RNA replicon particles Mice: 75-100% protection with Strain 2 guinea pigs (2 No protection with (VRP encoding: SC 2 x 106 FFU of VRP/EBOV NP [22-24] doses): no protection with VRP/EBOV GP or NP or EBOV NP [21-24] VRP/EBOV NP3 doses 90–100% protection with VRP-EBOV NP; 60% both immunogens [21] EBOV GP [21, 23-26] [22] VRP/EBOV GP [23-25] protection with VRP-EBOV Viremia present in all EBOV GP +NP[21, 23] SC 2 x 106 FFU or 2 x 106 Complete protection with GP [23] subjects EBOV VP24 [24, 27] IU of VRP/EBOV NP, VRP/EBOV GP+NP [23] Strain 13 guinea pigs (3 Time to death similar EBOV VP30 VP24, VP30, VP35, or 95–100% with VRP/EBOV VP doses): complete to controls EBOV VP35 VP40 for 2-3 doses [24, proteins in BALB/c mice[24] protection with VRP-EBOV EBOV VP40 27] 100% protection with NP+GP or VRP-EBOV GP; 6 EBOV GP + Lassa GP SC 1x10 IU of VRP/EBOV VRP/EBOV VP 30 or VP 35 20% protection with VRP- combination [26] GP, NP, or GP+NP for 2 proteins in C57BL/6 mice EBOV NP EBOV GP/Lassa GP doses [23] [24] 80% protection with 8 bivalent SC 1 x 10 of VRP EBOV 80% protection with bivalent VRP/EBOV GP with Lassa GP[26] GP- 4 doses [25] VRP/EBOV VP40 in C57BL/6 Guinea Pigs: mice [24] 100% protection with 7 SC 10 IU of VRP EBOV No protection with VRP/EBOV GP and GP, NP, or GP+NP–2 or 3 VRP/EBOV VP24 proteins in VRP/Lassa GP doses [23] C57BL/6 mice [24, 27] SC 107 IU of VRP EBOV Vaccines Immunization Schedule Mouse Model Guinea Pig Model NHP Model GP+Lassa GP-3 doses [26] NHPs: SC 2 x 106 FFU of VRP EBOV GP, NP or GP+NP–3 doses [21] KUN replicon encoding: Guinea Pigs: IP 1 x 106 or 5 x >75% protection with EBOV GP [28] 106 VLPs-2 doses KUN/GP or KUN/GP EBOV GP/Ctr mutant at higher dosage EBOV GP mutant for 50% protection with ease of shedding KUN/GP mutant at lower (D637L) dosage 25% protection with KUN/GP at lower dosage No protection with KUN/soluble GP rBV encoding: Mice: Dose dependent protection EBOV VP40 IM 1, 10 or 50 ug of rBV or with 2-dose regimen; EBOV GP [29] 293T cell derived/EBOV complete protection at rBV replicon encoding: VP40 + GP + NP VLPs–2 highest dose [29, 30] EBOV VP40 doses [30] 83% protection with 3 EBOV GP IM 10 or 50 µg of doses[29] EBOV NP [30] rBV/EBOV VP40 + GP Equivalent immune 293T cell-derived EBOV VLPs–2 doses [29] responses and protection VP40 + GP + NP [30] IM 10 ug of rBV/EBOV from challenge with rBV- VP40 GP VLPs–3 doses derived or 293T cell-derived VLPs[30] Liposomes encapsulating: Mice: IM, IP 0.1, 1, or 10 µg Complete or nearly Complete protection with Complete protection EBOV GP + VP40 [31-33] EBOV GP + VP40 VLPs for 2 complete protection with EBOV GP + VP40 VLPs [31] with EBOV EBOV NP+GP+VP40 [34, [33] or 3 doses [32] highest dosage EBOV GP + 90% protection with EBOV NP+GP+VP40 [35] 35] STAT-1 KO mice: IM 10 µg VP40 VLPs in BALB/c,[32] GP + MARV VP40 VLPs or Viremia and clinical or EBOV GP + MARV VP40 EBOV GP + VP40 + NP–3 C57Bl/6,or perforin- equal mixture of EBOV GP laboratory signs of [31] doses [34] deficient mice [33] + VP40 and MARV GP + EBOV infection not EBOV VP40 +MARV GP Guinea Pigs: 50% protection in CD4+- VP40 VLPs detected in vaccinated Vaccines Immunization Schedule Mouse Model Guinea Pig Model NHP Model MARV GP + VP40 IM 100 µg of EBOV GP + deficient mice No protection with EBOV and challenged NHPs VP40 VLPs [31] 13% protection in IFN-γ- VP40 +MARV GP Strong antibody and T IM 50 µg EBOV GP + VP40 deficient mice High antibody titers and cells (tumor necrosis and 50 µg MARV GP + No protection in B cell-, βδ no viremia in survivors factor-α) responses VP40 VLPs TCR-, CD8+-, or STAT-1- NHPs: IM 250 µg EBOV NP + deficient mice[33, 34] GP + VP40 VLPs in RIBI adjuvant–3 doses [35] DNA Vaccines DNA Plasmid Immunogens Mice: Complete protection with Complete protection with EBOV GP [36-40] Prime-0.5 µg of EBOV GP EBOV GP DNA prime/boost EBOV GP DNA alone[38, EBOV GP glycosylation DNA, then 3 boosts with [36] 39] or in combination deletions[37] 1.5 µg via gene gun [36] Similar dose-dependent with NP, or EBOV NP in EBOV sGP[39] 0.5 or 3 µg of EBOV NP or partial protection (~60– combination with TAFV EBOV NP [36, 39, 40] GP DNA via gene gun–3 90%) with either EBOV NP GP, EBOV GP SUDV GP EBOV GP + NP [38] doses [36] or GP DNA with boosts[36] and EBOV GP DNA[38] EBOV GP + TAFV GP+ 0.25–0.5 ug EBOV GP and 89% protection with EBOV Complete protection with SUDV GP + EBOV NP glycosylation mutants DNA GP DNA [37] EBOV NP or GP DNA and EBOV GP, Marv GP, via gene gun–3 doses [37] 29–31% protection with 83% protection with EBOV VEEV 26s, Anthrax PA 5 ug EBOV GP or NP DNA deletion