Immunogenicity of Recombinant Vesicular Stomatitis Vaccine for Ebola-Zaire (rVSV∆G-ZEBOV-GP Vaccine)

Summary

Background: The Ebola virus causes a severe disease that can be fatal. The usual incubation period to illness after being exposed is 2 to 21 days. There are only limited treatments currently available for Ebola infection. A vaccine to prevent infection either before or after exposure was approved in 2020 but the durability of the vaccine response is unknown. Researchers wish to study the potential to increase the antibody response to the licensed Ebola vaccine. An improved response before exposure to the virus potentially could increase the vaccine's effectiveness in preventing disease. Objectives: To see if the antibody response to the vaccine, rVSV∆G-ZEBOV-GP vaccine (V920), could potentially be improved by providing a booster injection several months after the primary immunization. Eligibility: Healthy adults at risk of exposure to the Ebola virus at work through lab or clinical contact. Design: * Participants will be screened with medical history, physical exam, and blood tests. * Participants will get the study vaccine. It will be injected into their upper arm. * Participants will be monitored closely for at least 30 minutes. They will get a diary card to record any symptoms they have from the vaccine for up to 14 days. * Participants will have study visits at 1, 3, and 6 months after they get the vaccine, then every 6 months (that is, at months 12, 18, 19, 24, 30, and 36 of study) for a total of 36 months. * Eighteen months after they join the study, participants will be randomly assigned to one of two groups. One group will get a second (or booster) dose of the vaccine. The other group will not get a second dose. * This study lasts 36 months. In December 2024, the study was approved to re-enroll up to 30 participants from the primary cohort to check longer-term immune response to the study vaccine beyond 36 months.

Timeline

Start

2016-10-14

Primary completion

2025-06-17

Completion

2025-06-17

Outcome

Met primary endpoint

paper was still over 7-fold higher at month 36 (GMR 7·8; 95% CI 5·5-10·2; p<0·0001). PMID 39374605 ↗

Publications

• Background Regules JA, Beigel JH, Paolino KM, Voell J, Castellano AR, Hu Z, Munoz P, Moon JE, Ruck RC, Bennett JW, Twomey PS, Gutierrez RL, Remich SA, Hack HR, Wisniewski ML, Josleyn MD, Kwilas SA, Van Deusen N, Mbaya OT, Zhou Y, Stanley DA, Jing W, Smith KS, Shi M, Ledgerwood JE, Graham BS, Sullivan NJ, Jagodzinski LL, Peel SA, Alimonti JB, Hooper JW, Silvera PM, Martin BK, Monath TP, Ramsey WJ, Link CJ, Lane HC, Michael NL, Davey RT Jr, Thomas SJ; rVSVDeltaG-ZEBOV-GP Study Group. A Recombinant Vesicular Stomatitis Virus Ebola Vaccine. N Engl J Med. 2017 Jan 26;376(4):330-341. doi: 10.1056/NEJMoa1414216. Epub 2015 Apr 1.
• Background Agnandji ST, Huttner A, Zinser ME, Njuguna P, Dahlke C, Fernandes JF, Yerly S, Dayer JA, Kraehling V, Kasonta R, Adegnika AA, Altfeld M, Auderset F, Bache EB, Biedenkopf N, Borregaard S, Brosnahan JS, Burrow R, Combescure C, Desmeules J, Eickmann M, Fehling SK, Finckh A, Goncalves AR, Grobusch MP, Hooper J, Jambrecina A, Kabwende AL, Kaya G, Kimani D, Lell B, Lemaitre B, Lohse AW, Massinga-Loembe M, Matthey A, Mordmuller B, Nolting A, Ogwang C, Ramharter M, Schmidt-Chanasit J, Schmiedel S, Silvera P, Stahl FR, Staines HM, Strecker T, Stubbe HC, Tsofa B, Zaki S, Fast P, Moorthy V, Kaiser L, Krishna S, Becker S, Kieny MP, Bejon P, Kremsner PG, Addo MM, Siegrist CA. Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe. N Engl J Med. 2016 Apr 28;374(17):1647-60. doi: 10.1056/NEJMoa1502924. Epub 2015 Apr 1.
• Results Davey RT Jr, Collins GL, Rouphael N, Poliquin G, McConnell R, Grubbs G, Moir SL, Langley JM, Teitelbaum M, Hewlett AL, McLellan SLF, Bhadelia N, Raabe VN, Mulligan MJ, Maljkovic Berry I, Dighero-Kemp B, Kurtz JR, Hensley LE, Dozier NCE, Marron LCB, DuChene A, Kuhn JH, Brown SK, Khurana S, Lane HC, Neaton JD. Safety and immunogenicity of a delayed booster dose of the rVSVDeltaG-ZEBOV-GP vaccine for prevention of Ebola virus disease: a multicentre, open-label, phase 2 randomised controlled trial. Lancet Microbe. 2024 Nov;5(11):100923. doi: 10.1016/S2666-5247(24)00163-0. Epub 2024 Oct 4.
• Raabe V, Lai L, Morales J, Xu Y, Rouphael N, Davey RT, Mulligan MJ. Cellular and humoral immunity to Ebola Zaire glycoprotein and viral vector proteins following immunization with recombinant vesicular stomatitis virus-based Ebola vaccine (rVSVDeltaG-ZEBOV-GP). Vaccine. 2023 Feb 17;41(8):1513-1523. doi: 10.1016/j.vaccine.2023.01.059. Epub 2023 Jan 31.

Drugs

Indications

No indication recorded.