Table 3.
EVD candidate vaccines in phase I–III clinical trials
| Candidate vaccine(s) | Vaccine design | Study design | Outcomes | Results | Notes | Trial |
|---|---|---|---|---|---|---|
| rVSVΔG-ZEBOV-GP (also known as BPSC-1001 and V920) | Replication-competent rVSIV expressing EBOV GP1,2 in place of VSIV G | Phase I trial evaluating safety and immunogenicity of rVSVΔG-ZEBOV-GP escalating doses | Primary: adverse effects up to 6 months. Secondary: humoral immunity up to 6 months | No pre-existing immunity; anti-EBOV matrix antibodies detected in 28% of participants, with levels that peaked at day 56 after vaccination289; neutralizing antibodies persisted for 6 months | Adverse effects: arthralgia, oligoarthritis, myalgia, headache and injection site pain | NCT02283099 |
| rAd26 ZEBOV-GP and MVA-BN-Filo | Replication-defective human adenovirus (Ad) 26 vector expressing EBOV GP1,2; replication-incompetent modified vaccinia virus Ankara (MVA) Bavarian Nordic (BN) expressing EBOV, SUDV, MARV and TAFV GP1,2 | Phase I trial evaluating safety and immunogenicity of MVA-BN-Filo and rAd26 ZEBOV-GP as heterologous prime-boost vaccine regimens | Primary: adverse effects up to 78 days. Secondary: immune responses up to 1 year | Anti-EBOV GP antibodies detected in 97% or 23% of participants receiving rAd26 ZEBOV-GP or MVA-BN-Filo, respectively, at 28 days after primary vaccination; all participants had specific IgG response at 21 days after the boost and at 8 months290 | Adverse effects: with rAd26 ZEBOV-GP: fever, injection site reactions headache, myalgia, nausea, fatigue and chills; with MVA-BN-Filo: injection site reactions, fatigue, headache, myalgia, chills, nausea, arthralgia, pruritus and rash | NCT02313077 |
| rVSVΔG-ZEBOV-GP (also known as BPSC-1001 and V920) | Replication-competent rVSIV expressing EBOV GP1,2 in place of VSIV G | Phase I/II trial evaluating safety and tolerability of rVSVΔG-ZEBOV-GP at low (3 × 105 pfu) or high (1–5 × 107 pfu) dose in health-care workers | Primary: adverse effects up to 14 days. Secondary: viraemia for 7 days, persistent titres of rVSVΔG-ZEBOV-GP-specific IgG antibodies at 168 days, neutralizing antibodies and rVSVΔG-ZEBOV-GP viral shedding up to 7 days291 | Anti-EBOV-GP binding and neutralizing antibody titres were lower in the low-dose group than in the high-dose group | Adverse effects: fever, myalgia and chills; oligoarthritis, maculopapular rash and vascular dermatitis in the low-dose group | NCT02287480, conducted in Switzerland |
| rVSVΔG-ZEBOV-GP (also known as BPSC-1001 and V920) or ChAd3-EBOZ | Replication-competent rVSIV expressing EBOV GP1,2 in place of VSIV G; ChAd3 vector expressing EBOV GP1,2 | Phase II trial comparison of vaccines and placebo | Primary outcome: serious adverse effects occurring within 30 days | With rVSVΔG-ZEBOV-GP: malaria, injection site reactions, headache, muscle pain, fever and fatigue | With rVSVΔG-ZEBOV-GP: geometric mean antibody titre maintained at 12 months at 800 ELISA units per ml | NCT02344407, also known as PREVAIL I, conducted in Liberia292 |
| rVSVΔG-ZEBOV-GP (also known as BPSC-1001 and V920) | Replication-competent rVSIV expressing EBOV GP1,2 in place of VSIV G | Phase II/III trial. Arm 1: immediate IM vaccination in patients with suspected EVD within 7 days of enrolment. Arm 2: deferred IM vaccination 18–24 weeks following enrolment, then crossed over to immediate vaccination group and monitored for 6 additional months | Primary: incidence of confirmed EBOV infections at >21 days after vaccination. Secondary: confirmed EBOV infections during 6 months following vaccination | No confirmed EBOV infections occurred; no efficacy analysis performed | Adverse events: fever, headache, fatigue, joint pain, rash and mouth ulcers293 | NCT02378753, also known as STRIVE, conducted in Sierra Leone |
| rVSVΔG-ZEBOV-GP (also known as BPSC-1001 and V920) | Replication-competent rVSIV expressing EBOV GP1,2 in place of VSIV G | Single-arm, phase IIIb study of ring vaccination (immediate and delayed) of contacts and contacts of contacts, given immediately after laboratory confirmation of initial case or after a delay of 21 days | Primary: number of patients with EVD amongst vaccinated (immediate and delayed) individuals. Secondary: assessment of safety 84 days after vaccination | No EVD cases within 10 days after immediate vaccination124; in delayed vaccination group, 23 patients with EVD out of 4,507 contacts | Adverse effects: headache, muscle pain, fever and anaphylaxis; potential neurotropism of VSIV may persist despite substitution of G with EBOV GP1,2294,295 | NCT03161366 and Ebola ça Suffit! trial |
| rVSVΔG-ZEBOV-GP (also known as BPSC-1001 and V920) | Replication-competent rVSIV expressing EBOV GP1,2 in place of VSIV G | Phase III trial evaluating safety and immunogenicity of rVSVΔG-ZEBOV-GP in healthy adults | Primary: determination of geometric mean titre of anti-EBOV GP1,2 antibodies at 28 days after vaccination and selected adverse events | Geometric mean titre of rVSVΔG-ZEBOV-GP (measured with ELISA) increased on day 28 and persisted through 24 months296; geometric mean titres of neutralizing antibodies peaked at 18 months and maintained at 24 months | Adverse effects: arthralgia and arthritis | NCT02503202 |
| rAd26 ZEBOV-GP and MVA-BN-Filo | Replication-defective human Ad 26 vector expressing EBOV GP1,2; replication-incompetent MVA-BN expressing EBOV, SUDV, MARV and TAFV GP1,2 | Phase III trial evaluating safety and immunogenicity of rAd26 ZEBOV-GP, MVA-BN-Filo boost 56 days after first vaccination and a second boost with rAd26 ZEBOV-GP given 2 years after the first vaccination | Primary: number of participants with adverse effects. Secondary: number of participants with adverse effects following the MVA-BN-Filo boost; serum concentrations of antibodies binding to EBOV GP1,2 after the MVA-BN-Filo boost | No efficacy data available as the outbreak in Sierra Leone ended before efficacy could be determined | Preliminary safety and immunogenicity follow-up data from EBOVAC Salone trial indicate that the vaccine regimen is well tolerated and produces immune responses up to 2 years after vaccination | NCT02509494, also known as EBOVAC-Salone |
| rAd26 ZEBOV-GP and MVA-BN-Filo | Replication-defective human Ad 26 vector expressing EBOV GP1,2; replication-incompetent MVA-BN expressing EBOV, SUDV, MARV and TAFV GP1,2 | Long-term safety and immunogenicity evaluation of previously vaccinated individuals. Cohort 1: participants who received at least a primary vaccination with rAd26 ZEBOV-GP and, if applicable, a MVA-BN-Filo boost 56 days after primary vaccination in healthy participants of ≥1 year of age. Cohort 2: infants conceived by participants in the 3 months following primary vaccination or 28 days following MVA-BN-Filo boost | Primary: number of participants with serious adverse effects and serum concentrations of EBOV GP1,2 up to 4–5 years following primary vaccination; in infants conceived during the trial, number of serious adverse effects from birth through 5 years of age. Secondary: anti-EBOV GP1,2 neutralizing antibodies 4–5 years after primary vaccination; effect of previous infection with Plasmodium spp. on persistence of humoral immune response to vaccination | Preliminary immunogenicity data indicate vaccine regimen produces immune responses up to 2 years after vaccination | Preliminary safety data indicate that the vaccine regimen is well tolerated | NCT03820739, also known as EBOVAC-Salone extension |
| rAd26 ZEBOV-GP, MVA-BN-Filo and rVSV ∆G-ZEBOV-GP | Replication-defective human Ad 26 vector expressing EBOV GP1,2; replication-incompetent MVA-BN expressing EBOV, SUDV, MARV and TAFV GP1,2; replication-competent rVSIV expressing EBOV GP1,2 in place of VSIV G | Phase III trial evaluating immunogenic equivalence. Arm 1: prime dose of rAd26 ZEBOV-GP, then boost dose of MVA-BN-Filo given after 8 weeks in healthy individuals of ≥1 year of age. Arm 2: single dose of rVSV∆G-ZEBOV-GP. Arm 3: two doses of rVSV∆G-ZEBOV-GP given 8 weeks apart | Primary: number of participants with anti-EBOV GP1,2 response through month 12. Secondary: number of participants with serious adverse effects | No published efficacy data | No published safety data | NCT02543268 and NCT02876328, also known as PREVAC, conducted in Guinea, Liberia, Sierra Leone and Mali |
| rAd26 ZEBOV-GP and MVA-BN-Filo | Replication-defective human Ad 26 vector expressing EBOV GP1,2; replication-incompetent MVA-BN expressing EBOV, SUDV, MARV and TAFV GP1,2 | Persistence of immune response 24–60 months after primary vaccination in phase I/II studies participants who received prime-boost rAd26 ZEBOV-GP and MVA-BN-Filo vaccines or individuals who received rVSVΔG-ZEBOV-GP vaccine alone | Primary: antibody binding to EBOV GP1,2 antigen. Secondary: pro-inflammatory cytokine response of T cells and IFNɣ release by activated T cells | T cell-initiated cytokine release and anti-EBOV GP1,2-specific antibody responses were present at 360 days following prime with rAd26 ZEBOV-GP then MVA-BN-Filo boost on day 57 after vaccination297 | Limitations: conducted in European population; immune responses may differ in African population | NCT03140774; conducted in the UK |
This table is not a comprehensive list of candidate vaccines that were tested in phase I–III clinical trials. Some candidate vaccines did not progress to more advanced phases or were used in outbreak settings. For more information on clinical trials of these vaccines, refer to ClinicalTrials.gov. EBOV, Ebola virus; EVD, Ebola virus disease; GP, glycoprotein; IM, intramuscular; MARV, Marburg virus; pfu, plaque-forming units; SUDV, Sudan virus; TAFV, Taï Forest virus; VSIV, vesicular stomatitis Indiana virus; ZEBOV, Zaire ebolavirus.