1. Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe.
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Agnandji, S. T., Huttner, A., Zinser, M. E., Njuguna, P., Dahlke, C., Fernandes, J. F., Yerly, S., Dayer, J. -A., Kraehling, V., Kasonta, R., Adegnika, A. A., Altfeld, M., Auderset, F., Bache, E. B., Biedenkopf, N., Borregaard, S., Brosnahan, J. S., Burrow, R., Combescure, C., and Desmeules, J.
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EBOLA virus disease vaccines , *EBOLA virus disease , *STOMATITIS , *GLYCOPROTEINS , *VIREMIA , *PATIENTS , *EBOLA virus disease prevention , *ARTHRITIS , *CLINICAL trials , *COMPARATIVE studies , *EXANTHEMA , *RESEARCH methodology , *MEDICAL cooperation , *PROTEINS , *RECOMBINANT proteins , *RESEARCH , *RESEARCH funding , *SKIN inflammation , *VIRAL antibodies , *VIRAL vaccines , *VIRAL physiology , *EVALUATION research , *RANDOMIZED controlled trials , *BLIND experiment , *MEMBRANE glycoproteins , *EBOLA virus - Abstract
Background: 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.Methods: 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.Results: 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.Conclusions: 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.). [ABSTRACT FROM AUTHOR]- Published
- 2016
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