Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe
BACKGROUND<br/> 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. <br/><br/>METHODS<br/> We performed...
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| Format: | Journal article |
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Massachusetts Medical Society
2016
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| author | Agnandji, S Huttner, A Zinser, M Bejon, P |
| author_facet | Agnandji, S Huttner, A Zinser, M Bejon, P |
| author_sort | Agnandji, S |
| collection | OXFORD |
| description | BACKGROUND<br/> 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. <br/><br/>METHODS<br/> 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. <br/><br/>RESULTS<br/> 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. <br/><br/>CONCLUSIONS<br/> In these studies, rVSV-ZEBOV was reactogenic but immunogenic after a single dose and warrants further evaluation for safety and efficacy. |
| first_indexed | 2024-03-06T23:28:27Z |
| format | Journal article |
| id | oxford-uuid:6b35ee09-7e09-4908-a98d-ded6a2f6cf7c |
| institution | University of Oxford |
| last_indexed | 2024-03-06T23:28:27Z |
| publishDate | 2016 |
| publisher | Massachusetts Medical Society |
| record_format | dspace |
| spelling | oxford-uuid:6b35ee09-7e09-4908-a98d-ded6a2f6cf7c2022-03-26T19:02:21ZPhase 1 Trials of rVSV Ebola Vaccine in Africa and EuropeJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6b35ee09-7e09-4908-a98d-ded6a2f6cf7cSymplectic Elements at OxfordMassachusetts Medical Society2016Agnandji, SHuttner, AZinser, MBejon, PBACKGROUND<br/> 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. <br/><br/>METHODS<br/> 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. <br/><br/>RESULTS<br/> 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. <br/><br/>CONCLUSIONS<br/> In these studies, rVSV-ZEBOV was reactogenic but immunogenic after a single dose and warrants further evaluation for safety and efficacy. |
| spellingShingle | Agnandji, S Huttner, A Zinser, M Bejon, P Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe |
| title | Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe |
| title_full | Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe |
| title_fullStr | Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe |
| title_full_unstemmed | Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe |
| title_short | Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe |
| title_sort | phase 1 trials of rvsv ebola vaccine in africa and europe |
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