Title |
Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe
|
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Published in |
New England Journal of Medicine, April 2015
|
DOI | 10.1056/nejmoa1502924 |
Pubmed ID | |
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 |
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 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 35% of vaccinees. Vaccine viremia was detected within 3 days in 103 of 110 participants (94%) 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; 2 self-limited cases occurred in 40 participants (5%) 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. 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 .). |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 13 | 19% |
United Kingdom | 4 | 6% |
Spain | 2 | 3% |
Kenya | 2 | 3% |
Colombia | 2 | 3% |
Brazil | 2 | 3% |
Japan | 2 | 3% |
Switzerland | 2 | 3% |
Italy | 1 | 1% |
Other | 11 | 16% |
Unknown | 28 | 41% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 51 | 74% |
Scientists | 8 | 12% |
Practitioners (doctors, other healthcare professionals) | 6 | 9% |
Science communicators (journalists, bloggers, editors) | 4 | 6% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 3 | <1% |
United States | 2 | <1% |
Japan | 2 | <1% |
Ireland | 1 | <1% |
South Africa | 1 | <1% |
Vietnam | 1 | <1% |
Germany | 1 | <1% |
Sierra Leone | 1 | <1% |
Unknown | 498 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 82 | 16% |
Student > Master | 74 | 15% |
Student > Bachelor | 70 | 14% |
Student > Ph. D. Student | 59 | 12% |
Other | 38 | 7% |
Other | 85 | 17% |
Unknown | 102 | 20% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 122 | 24% |
Agricultural and Biological Sciences | 66 | 13% |
Biochemistry, Genetics and Molecular Biology | 49 | 10% |
Immunology and Microbiology | 39 | 8% |
Nursing and Health Professions | 27 | 5% |
Other | 80 | 16% |
Unknown | 127 | 25% |