Immunogenicity and safety of ebolavirus vaccines in healthy adults: a systematic review and meta-analysis of randomized controlled trials

References

• Piot P, Spencer J. From 1976 to 2018: reflections on early investigations into the Ebola virus. Trans R Soc Trop Med Hyg. 2018 Dec 1;112(12):527–528. doi: 10.1093/trstmh/try088
   PubMed Web of Science ®Google Scholar
• WHO. Ebola virus disease 2022. Available from: https://www.who.int/health-topics/ebola#tab=tab_1
   Google Scholar
• Kim YE. Child mortality after the Ebola virus disease outbreak across Guinea, Liberia, and Sierra Leone. Int J Infect Dis. 2022 Sep;122:944–952. doi: 10.1016/j.ijid.2022.06.043
   PubMed Web of Science ®Google Scholar
• Luo Y, Song C, Zhang H, et al. Toward sustainable and effective control: experience of China Ebola treatment center in Liberia. J Microbiol Immunol Infect. 2017 Feb;50(1):1–3.
   PubMedGoogle Scholar
• Anywaine Z, Barry H, Anzala O, et al. Safety and immunogenicity of 2-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccination in children and adolescents in Africa: a randomised, placebo-controlled, multicentre phase II clinical trial. PLOS Med. 2022;19(1):e1003865. doi: 10.1371/journal.pmed.1003865
   PubMed Web of Science ®Google Scholar
• Henao-Restrepo AM, Camacho A, Longini IM, et al. Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!). Lancet. 2017 Feb 4;389(10068):505–518. doi: 10.1016/S0140-6736(16)32621-6
   PubMed Web of Science ®Google Scholar
• Ishola D, Manno D, Afolabi MO, et al. Safety and long-term immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in adults in Sierra Leone: a combined open-label, non-randomised stage 1, and a randomised, double-blind, controlled stage 2 trial. Lancet Infect Dis. 2022 Jan;22(1):97–109.
   PubMed Web of Science ®Google Scholar
• Nyombayire J, Ingabire R, Magod B, et al. Monitoring of adverse events in recipients of the 2-dose Ebola vaccine regimen of Ad26.ZEBOV followed by MVA-BN-Filo in the UMURINZI Ebola vaccination campaign. J Infect Dis. 2023 Jan 11;227(2):268–277. doi: 10.1093/infdis/jiac283
   PubMed Web of Science ®Google Scholar
• Mulangu S, Dodd LE, Davey RT Jr., et al. A randomized, controlled trial of Ebola virus disease therapeutics. N Engl J Med. 2019 Dec 12;381(24):2293–2303. doi: 10.1056/NEJMoa1910993
   PubMed Web of Science ®Google Scholar
• Fuentes S, Ravichandran S, Coyle EM, et al. Human antibody repertoire following Ebola virus infection and vaccination. iScience. 2020 Mar 27;23(3):100920. doi: 10.1016/j.isci.2020.100920
   PubMed Web of Science ®Google Scholar
• Goldstein N, Bockstal V, Bart S, et al. Safety and immunogenicity of heterologous and homologous 2-dose regimens of adenovirus serotype 26- and modified vaccinia ankara-vectored Ebola vaccines: a randomized, controlled phase 1 study. J Infect Dis. 2022 Sep 4;226(4):595–607. doi: 10.1093/infdis/jiaa586
   PubMed Web of Science ®Google Scholar
• Diallo A, Carlos-Bolumbu M, Cervantes-Gonzalez M, et al. Immunogenicity and safety of Ebola virus vaccines in healthy adults: a systematic review and network meta-analysis. Hum Vaccin Immunother. 2021 Oct 3;17(10):3771–3783. doi: 10.1080/21645515.2021.1932214
   PubMed Web of Science ®Google Scholar
• Higgins JPT, Sally G. Cochrane handbook for systematic reviews of interventions. (New Jersey): Wiley; 2008.
   Google Scholar
• Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021 Mar 29;372:n71. doi: 10.1136/bmj.n71
   PubMedGoogle Scholar
• Julian H, Lasserson T, Jackie C, et al. Standards for the conduct and reporting of new Cochrane intervention reviews, reporting of protocols and the planning, conduct and reporting of updates: Cochrane. 2022. Available from: http://community.cochrane.org/mecir-manual
   Google Scholar
• Hartung J, Knapp G. A refined method for the meta-analysis of controlled clinical trials with binary outcome. Stat Med. 2001 Dec 30;20(24):3875–89. doi: 10.1002/sim.1009
   PubMed Web of Science ®Google Scholar
• DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986 Sep;7(3):177–188. doi: 10.1016/0197-2456(86)90046-2
   PubMedGoogle Scholar
• Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997 Sep 13;315(7109):629–634. doi: 10.1136/bmj.315.7109.629
   PubMedGoogle Scholar
• Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019 Aug 28;366:l4898. doi: 10.1136/bmj.l4898
   PubMedGoogle Scholar
• Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008 Apr 26;336(7650):924–926. doi: 10.1136/bmj.39489.470347.AD
   PubMedGoogle Scholar
• Higgins JPT, Thomas J, Chandler J, et al. Interpreting results and drawing conclusions. In: Cochrane handbook for systematic reviews of interventions. Chichester (UK): John Wiley & Sons; 2019.
   Google Scholar
• Krause PR. Interim results from a phase 3 Ebola vaccine study in Guinea. Lancet. 2015 Aug 29;386(9996):831–833. doi: 10.1016/S0140-6736(15)00002-1
   PubMed Web of Science ®Google Scholar
• Agnandji ST, Fernandes JF, Bache EB, et al. Safety and immunogenicity of rVsvδG-ZEBOV-GP Ebola vaccine in adults and children in Lambaréné, Gabon: a phase I randomised trial. PLOS Med. 2017 Oct;14(10):e1002402.
   PubMed Web of Science ®Google Scholar
• Dolzhikova IV, Zubkova OV, Tukhvatulin AI, et al. Safety and immunogenicity of GamEvac-Combi, a heterologous VSV- and Ad5-vectored Ebola vaccine: an open phase I/II trial in healthy adults in Russia. Hum Vaccin Immunother. 2017 Mar 4;13(3):613–620. doi: 10.1080/21645515.2016.1238535
   PubMed Web of Science ®Google Scholar
• Wu L, Zhang Z, Gao H, et al. Open-label phase I clinical trial of Ad5-EBOV in Africans in China. Hum Vaccin Immunother. 2017 Sep 2;13(9):2078–2085. doi: 10.1080/21645515.2017.1342021
   PubMed Web of Science ®Google Scholar
• Afolabi MO, Ishola D, Manno D, et al. Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in children in Sierra Leone: a randomised, double-blind, controlled trial. Lancet Infect Dis. 2022 Jan;22(1):110–122.
   PubMed Web of Science ®Google Scholar
• Tapia MD, Sow SO, Mbaye KD, et al. Safety, reactogenicity, and immunogenicity of a chimpanzee adenovirus vectored Ebola vaccine in children in Africa: a randomised, observer-blind, placebo-controlled, phase 2 trial. Lancet Infect Dis. 2020 Jun;20(6):719–730.
   PubMed Web of Science ®Google Scholar
• Manno D, Bangura A, Baiden F, et al. Safety and immunogenicity of an Ad26.ZEBOV booster dose in children previously vaccinated with the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen: an open-label, non-randomised, phase 2 trial. Lancet Infect Dis. 2023 Mar;23(3):352–360.
   PubMed Web of Science ®Google Scholar
• De Santis O, Audran R, Pothin E, et al. Safety and immunogenicity of the Chimpanzee-Adenovirus vectored Ebola vaccine: the lausanne phase I/IIa clinical trial. Trop Med Int Health. 2015;20:43.
   Web of Science ®Google Scholar
• Simon JK, Kennedy SB, Mahon BE, et al. Immunogenicity of rVsvδG-ZEBOV-GP Ebola vaccine (ERVEBO®) in African clinical trial participants by age, sex, and baseline GP-ELISA titer: a post hoc analysis of three phase 2/3 trials. Vaccine. 2022 Nov 2;40(46):6599–6606. doi: 10.1016/j.vaccine.2022.09.037
   PubMed Web of Science ®Google Scholar
• Agnandji ST, Huttner A, Zinser ME, et al. Phase 1 trials of rVSV Ebola vaccine in Africa and Europe. New Engl J Med. 2016;374(17):1647‐1660. doi: 10.1056/NEJMoa1502924
   PubMed Web of Science ®Google Scholar
• Anywaine Z, Whitworth H, Kaleebu P, et al. Safety and immunogenicity of a 2-dose heterologous vaccination regimen with Ad26.ZEBOV and MVA-BN-Filo Ebola vaccines: 12-month data from a phase 1 randomized clinical trial in Uganda and Tanzania. J Infect Dis. 2019 Jun 5;220(1):46–56. doi: 10.1093/infdis/jiz070
   PubMed Web of Science ®Google Scholar
• Barry H, Mutua G, Kibuuka H, et al. Safety and immunogenicity of 2-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccination in healthy and HIV-infected adults: a randomised, placebo-controlled phase II clinical trial in Africa. PLOS Med. 2021 Oct;18(10):e1003813.
   PubMed Web of Science ®Google Scholar
• Bockstal V, Shukarev G, McLean C, et al. First-in-human study to evaluate safety, tolerability, and immunogenicity of heterologous regimens using the multivalent filovirus vaccines Ad26.Filo and MVA-BN-Filo administered in different sequences and schedules: a randomized, controlled study. PLoS One. 2022 Oct 5;17(10):e0274906. doi: 10.1371/journal.pone.0274906
   PubMed Web of Science ®Google Scholar
• Clarke DK, Xu R, Matassov D, et al. Safety and immunogenicity of a highly attenuated rVSVN4CT1-EBOVGP1 Ebola virus vaccine: a randomised, double-blind, placebo-controlled, phase 1 clinical trial. Lancet Infect Dis. 2020 Apr;20(4):455–466.
   PubMed Web of Science ®Google Scholar
• De Santis O, Audran R, Pothin E, et al. Safety and immunogenicity of a chimpanzee adenovirus-vectored Ebola vaccine in healthy adults: a randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a study. Lancet Infect Dis. 2016 Mar;16(3):311–20.
   PubMed Web of Science ®Google Scholar
• ElSherif MS, Brown C, MacKinnon-Cameron D, et al. Assessing the safety and immunogenicity of recombinant vesicular stomatitis virus Ebola vaccine in healthy adults: a randomized clinical trial. Can Med Assoc J. 2017 Jun 19;189(24):E819‐E827. doi: 10.1503/cmaj.170074
   Web of Science ®Google Scholar
• Fries L, Cho I, Krähling V, et al. Randomized, blinded, dose-ranging trial of an Ebola virus glycoprotein nanoparticle vaccine with matrix-M adjuvant in healthy adults. J Infect Dis. 2020 Jul 23;222(4):572‐582. doi: 10.1093/infdis/jiz518
   PubMed Web of Science ®Google Scholar
• Halperin SA, Arribas JR, Rupp R, et al. Six-month Safety data of recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine in a phase 3 double-blind, placebo-controlled randomized study in healthy adults. J Infect Dis. 2017 Jun 15;215(12):1789‐1798. doi: 10.1093/infdis/jix189
   Web of Science ®Google Scholar
• Halperin SA, Das R, Onorato MT, et al. Immunogenicity, lot consistency, and extended Safety of rVsvδG-ZEBOV-GP vaccine: a phase 3 randomized, double-blind, placebo-controlled study in healthy adults. J Infect Dis. 2019 Aug 30;220(7):1127‐1135. doi: 10.1093/infdis/jiz241
   PubMed Web of Science ®Google Scholar
• Heppner DG Jr., Kemp TL, Martin BK, et al. Safety and immunogenicity of the rVsv∆G-ZEBOV-GP Ebola virus vaccine candidate in healthy adults: a phase 1b randomised, multicentre, double-blind, placebo-controlled, dose-response study. Lancet Infect Dis. 2017 Aug;17(8):854–866.
   PubMed Web of Science ®Google Scholar
• Huttner A, Dayer JA, Yerly S, et al. The effect of dose on the safety and immunogenicity of the VSV Ebola candidate vaccine: a randomised double-blind, placebo-controlled phase 1/2 trial. Lancet Infect Dis. 2015 Oct;15(10):1156‐1166.
   PubMed Web of Science ®Google Scholar
• Kennedy SB, Bolay F, Kieh M, et al. Phase 2 placebo-controlled trial of two vaccines to prevent Ebola in Liberia. New Engl J Med. 2017 Oct 12;377(15):1438‐1447. doi: 10.1056/NEJMoa1614067
   PubMed Web of Science ®Google Scholar
• Kibuuka H, Berkowitz NM, Millard M, et al. Safety and immunogenicity of Ebola virus and marburg virus glycoprotein DNA vaccines assessed separately and concomitantly in healthy Ugandan adults: a phase 1b, randomised, double-blind, placebo-controlled clinical trial. Lancet. 2015 Apr 18;385(9977):1545–1554. doi: 10.1016/S0140-6736(14)62385-0
   PubMed Web of Science ®Google Scholar
• Ledgerwood JE, Costner P, Desai N, et al. A replication defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults. Vaccine. 2010 Dec 16;29(2):304‐313. doi: 10.1016/j.vaccine.2010.10.037
   PubMed Web of Science ®Google Scholar
• Martin JE, Sullivan NJ, Enama ME, et al. A DNA vaccine for Ebola virus is safe and immunogenic in a phase I clinical trial. Clin Vaccine Immunol. 2006 Nov;13(11):1267–1277.
   PubMed Web of Science ®Google Scholar
• Milligan ID, Gibani MM, Sewell R, et al. Safety and immunogenicity of novel adenovirus type 26- and modified vaccinia ankara-vectored Ebola vaccines: a randomized clinical trial. JAMA. 2016 Apr 19;315(15):1610–1623. doi: 10.1001/jama.2016.4218
   PubMed Web of Science ®Google Scholar
• Mutua G, Anzala O, Luhn K, et al. Safety and immunogenicity of a 2-dose heterologous vaccine regimen with Ad26.ZEBOV and MVA-BN-Filo Ebola vaccines: 12-month data from a phase 1 randomized clinical trial in Nairobi, Kenya. J Infect Dis. 2019 Jun 5;220(1):57–67. doi: 10.1093/infdis/jiz071
   PubMed Web of Science ®Google Scholar
• Pollard AJ, Launay O, Lelievre JD, et al. Safety and immunogenicity of a two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in adults in Europe (EBOVAC2): a randomised, observer-blind, participant-blind, placebo-controlled, phase 2 trial. Lancet Infect Dis. 2021 Apr;21(4):493–506.
   PubMed Web of Science ®Google Scholar
• Regules JA, Beigel JH, Paolino KM, et al. A Recombinant Vesicular Stomatitis Virus Ebola Vaccine. N Engl J Med. 2017 Jan 26;376(4):330–341. doi: 10.1056/NEJMoa1414216
   PubMed Web of Science ®Google Scholar
• Samai M, Seward JF, Goldstein ST, et al. The Sierra Leone trial to introduce a vaccine against Ebola: an evaluation of rVsv∆G-ZEBOV-GP vaccine tolerability and Safety during the West Africa Ebola outbreak. J Infect Dis. 2018 May 18;217(suppl_1):S6‐S15. doi: 10.1093/infdis/jiy020
   Google Scholar
• Tapia MD, Sow SO, Lyke KE, et al. Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2016 Jan;16(1):31–42.
   PubMed Web of Science ®Google Scholar
• Tapia MD, Sow SO, Ndiaye BP, et al. Safety, reactogenicity, and immunogenicity of a chimpanzee adenovirus vectored Ebola vaccine in adults in Africa: a randomised, observer-blind, placebo-controlled, phase 2 trial. Lancet Infect Dis. 2020 Jun;20(6):707–718.
   PubMed Web of Science ®Google Scholar
• Zhu FC, Wurie AH, Hou LH, et al. Safety and immunogenicity of a recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in Sierra Leone: a single-centre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet (London, England). 2017 Feb 11;389(10069):621‐628. doi: 10.1016/S0140-6736(16)32617-4
   Web of Science ®Google Scholar
• Kieh M, Richert L, Beavogui AH, et al. Randomized trial of vaccines for Zaire Ebola virus disease. N Engl J Med. 2022 Dec 29;387(26):2411–2424.
   PubMed Web of Science ®Google Scholar
• Li JX, Hou LH, Meng FY, et al. Immunity duration of a recombinant adenovirus type-5 vector-based Ebola vaccine and a homologous prime-boost immunisation in healthy adults in China: final report of a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Glob Health. 2017 Mar;5(3):e324–e334.
   PubMed Web of Science ®Google Scholar
• Zhu FC, Hou LH, Li JX, et al. Safety and immunogenicity of a novel recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in China: preliminary report of a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet. 2015 Jun 6;385(9984):2272–2279. doi: 10.1016/S0140-6736(15)60553-0
   PubMed Web of Science ®Google Scholar
• Winokur P, Gayed J, Fitz-Patrick D, et al. Bivalent omicron BA.1-adapted BNT162b2 booster in adults older than 55 years. N Engl J Med. 2023 Jan 19;388(3):214–227. doi: 10.1056/NEJMoa2213082
   PubMed Web of Science ®Google Scholar
• Criado MF, Kassa A, Bertran K, et al. Efficacy of multivalent recombinant herpesvirus of turkey vaccines against high pathogenicity avian influenza, infectious bursal disease, and newcastle disease viruses. Vaccine. 2023 May 2;41(18):2893–2904. doi: 10.1016/j.vaccine.2023.03.055
   PubMed Web of Science ®Google Scholar
• Heath PT, Galiza EP, Baxter DN, et al. Safety and Efficacy of the NVX-CoV2373 coronavirus disease 2019 vaccine at completion of the placebo-controlled phase of a randomized controlled trial. Clin Infect Dis. 2023 Feb 8;76(3):398–407. doi: 10.1093/cid/ciac803
   PubMed Web of Science ®Google Scholar
• Reiter PL, Gower AL, Kiss DE, et al. Efficacy of the outsmart HPV intervention: a randomized controlled trial to increase HPV vaccination among young gay, bisexual, and other men who have sex with men. Cancer Epidemiol Biomarkers Prev. 2023 Jun 1;32(6):760–767. doi: 10.1158/1055-9965.EPI-23-0007
   PubMed Web of Science ®Google Scholar
• Doshi RH, Fleming M, Mukoka AK, et al. Vaccination of contacts of Ebola virus disease survivors to prevent further transmission. Lancet Glob Health. 2020 Dec;8(12):e1455–e1456.
   PubMed Web of Science ®Google Scholar
• Karita E, Nyombayire J, Ingabire R, et al. Safety, reactogenicity, and immunogenicity of a 2-dose Ebola vaccine regimen of Ad26.ZEBOV followed by MVA-BN-Filo in healthy adult pregnant women: study protocol for a phase 3 open-label randomized controlled trial. Trials. 2022 Jun 20;23(1):513. doi: 10.1186/s13063-022-06360-3
   PubMedGoogle Scholar
• Watson-Jones D, Kavunga-Membo H, Grais RF, et al. Protocol for a phase 3 trial to evaluate the effectiveness and safety of a heterologous, two-dose vaccine for Ebola virus disease in the Democratic Republic of the Congo. BMJ Open. 2022 Mar 8;12(3):e055596.10.1136/bmjopen-2021-055596
   PubMed Web of Science ®Google Scholar
• Higgins J, Thomas J, Chandler J, et al. Cochrane handbook for systematic reviews of Interventions version 6.2 (updated February 2021). Cochrane; 2022 [updated 2022 Aug 4; cited 2022]. Available from: https://community.cochrane.org/mecir-manual.
   Google Scholar