Dataset Information

Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe.

ABSTRACT: The replication-competent recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing a Zaire ebolavirus (ZEBOV) glycoprotein was selected for rapid safety and immunogenicity testing before its use in West Africa.We performed three open-label, dose-escalation phase 1 trials and one randomized, double-blind, controlled phase 1 trial to assess the safety, side-effect profile, and immunogenicity of rVSV-ZEBOV at various doses in 158 healthy adults in Europe and Africa. All participants were injected with doses of vaccine ranging from 300,000 to 50 million plaque-forming units (PFU) or placebo.No serious vaccine-related adverse events were reported. Mild-to-moderate early-onset reactogenicity was frequent but transient (median, 1 day). Fever was observed in up to 30% of vaccinees. Vaccine viremia was detected within 3 days in 123 of the 130 participants (95%) receiving 3 million PFU or more; rVSV was not detected in saliva or urine. In the second week after injection, arthritis affecting one to four joints developed in 11 of 51 participants (22%) in Geneva, with pain lasting a median of 8 days (interquartile range, 4 to 87); 2 self-limited cases occurred in 60 participants (3%) in Hamburg, Germany, and Kilifi, Kenya. The virus was identified in one synovial-fluid aspirate and in skin vesicles of 2 other vaccinees, showing peripheral viral replication in the second week after immunization. ZEBOV-glycoprotein-specific antibody responses were detected in all the participants, with similar glycoprotein-binding antibody titers but significantly higher neutralizing antibody titers at higher doses. Glycoprotein-binding antibody titers were sustained through 180 days in all participants.In these studies, rVSV-ZEBOV was reactogenic but immunogenic after a single dose and warrants further evaluation for safety and efficacy. (Funded by the Wellcome Trust and others; ClinicalTrials.gov numbers, NCT02283099, NCT02287480, and NCT02296983; Pan African Clinical Trials Registry number, PACTR201411000919191.).

SUBMITTER: Agnandji ST

PROVIDER: S-EPMC5490784 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe.

Agnandji Selidji T ST Huttner Angela A Zinser Madeleine E ME Njuguna Patricia P Dahlke Christine C Fernandes José F JF Yerly Sabine S Dayer Julie-Anne JA Kraehling Verena V Kasonta Rahel R Adegnika Akim A AA Altfeld Marcus M Auderset Floriane F Bache Emmanuel B EB Biedenkopf Nadine N Borregaard Saskia S Brosnahan Jessica S JS Burrow Rebekah R Combescure Christophe C Desmeules Jules J Eickmann Markus M Fehling Sarah K SK Finckh Axel A Goncalves Ana Rita AR Grobusch Martin P MP Hooper Jay J Jambrecina Alen A Kabwende Anita L AL Kaya Gürkan G Kimani Domtila D Lell Bertrand B Lemaître Barbara B Lohse Ansgar W AW Massinga-Loembe Marguerite M Matthey Alain A Mordmüller Benjamin B Nolting Anne A Ogwang Caroline C Ramharter Michael M Schmidt-Chanasit Jonas J Schmiedel Stefan S Silvera Peter P Stahl Felix R FR Staines Henry M HM Strecker Thomas T Stubbe Hans C HC Tsofa Benjamin B Zaki Sherif S Fast Patricia P Moorthy Vasee V Kaiser Laurent L Krishna Sanjeev S Becker Stephan S Kieny Marie-Paule MP Bejon Philip P Kremsner Peter G PG Addo Marylyn M MM Siegrist Claire-Anne CA

The New England journal of medicine 20150401 17

<h4>Background</h4>The replication-competent recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing a Zaire ebolavirus (ZEBOV) glycoprotein was selected for rapid safety and immunogenicity testing before its use in West Africa.<h4>Methods</h4>We performed three open-label, dose-escalation phase 1 trials and one randomized, double-blind, controlled phase 1 trial to assess the safety, side-effect profile, and immunogenicity of rVSV-ZEBOV at various doses in 158 healthy adults in Eu ...[more]

PMID: 25830326

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Project description:BACKGROUND:As part of a Phase III trial with the Ebola vaccine rVSV?G-ZEBOV-GP in Guinea, we invited frontline workers (FLWs) to participate in a sub-study to provide additional information on the immunogenicity of the vaccine. METHODS:We conducted an open-label, non-randomized, single-arm immunogenicity evaluation of one dose of rVSV?G-ZEBOV-GP among healthy FLWs in Guinea. FLWs who refused vaccination were offered to participate as a control group. We followed participants for 84 days with a subset followed-up for 180 days. The primary endpoint was immune response, as measured by ELISA for ZEBOV-glycoprotein-specific antibodies (ELISA-GP) at 28 days. We also conducted neutralization, whole virion ELISA and enzyme-linked immunospot (ELISPOT) assay for cellular response. RESULTS:A total of 1172 participants received one dose of vaccine and were followed-up for 84 days, among them 114 participants were followed-up for 180 days. Additionally, 99 participants were included in the control group and followed up for 180 days. Overall, 86.4% (95% CI 84.1-88.4) of vaccinated participants seroresponded at 28 days post-vaccination (ELISA- GP) with 65% of these seroresponding at 14 days post-vaccination. Among those who seroresponded at 28 days, 90.7% (95% CI 82.0-95.4) were still seropositive at 180 days. The proportion of seropositivity in the unvaccinated group was 0.0% (95% CI 0.0-3.8) at 28 days and 5.4% (95% CI 2.1-13.1) at 180 days post-vaccination. We found weak correlation between ELISA-GP and neutralization at baseline but significant pairwise correlation at 28 days post-vaccination. Among samples analysed for cellular response, only 1 (2.2%) exhibited responses towards the Zaire Ebola glycoprotein (Ebola GP ? 10) at baseline, 10 (13.5%) at day 28 post-vaccination and 27 (48.2%) at Day 180. CONCLUSIONS:We found one dose of rVSV?G-ZEBOV-GP to be highly immunogenic at 28- and 180-days post vaccination among frontline workers in Guinea. We also found a cellular response that increased with time.

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Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe.

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Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe.

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