Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe.
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| 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.).
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| Authors | Selidji T Agnandji, Angela Huttner, Madeleine E Zinser, Patricia Njuguna, Christine Dahlke, José F Fernandes, Sabine Yerly, Julie-Anne Dayer, Verena Kraehling, Rahel Kasonta, Akim A Adegnika, Marcus Altfeld, Floriane Auderset, Emmanuel B Bache, Nadine Biedenkopf, Saskia Borregaard, Jessica S Brosnahan, Rebekah Burrow, Christophe Combescure, Jules Desmeules, Markus Eickmann, Sarah K Fehling, Axel Finckh, Ana Rita Goncalves, Martin P Grobusch, Jay Hooper, Alen Jambrecina, Anita L Kabwende, Gürkan Kaya, Domtila Kimani, Bertrand Lell, Barbara Lemaître, Ansgar W Lohse, Marguerite Massinga-Loembe, Alain Matthey, Benjamin Mordmüller, Anne Nolting, Caroline Ogwang, Michael Ramharter, Jonas Schmidt-Chanasit, Stefan Schmiedel, Peter Silvera, Felix R Stahl, Henry M Staines, Thomas Strecker, Hans C Stubbe, Benjamin Tsofa, Sherif Zaki, Patricia Fast, Vasee Moorthy, Laurent Kaiser, Sanjeev Krishna, Stephan Becker, Marie-Paule Kieny, Philip Bejon, Peter G Kremsner, Marylyn M Addo, Claire-Anne Siegrist |
| Journal | The New England journal of medicine (N Engl J Med) Vol. 374 Issue 17 Pg. 1647-60 (Apr 28 2016) ISSN: 1533-4406 [Electronic] United States |
| PMID | 25830326 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.) |
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