Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial

Ana Maria Henao-Restrepo, Ira M. Longini, Matthias Egger, Natalie E. Dean, William Edmunds, Anton Camacho, Miles Carroll, Moussa Doumbia, Bertrand Draguez, Sophie Duraffour, Godwin Enwere, Rebecca Grais, Stephan Gunther, Stefanie Hossmann, Mandy Kader Kondé, Souleymane Kone, Eeva Kuisma, Myron M. Levine, Sema Mandal, Gunnstein NorheimXimena Riveros, Aboubacar Soumah, Sven Trelle, Andrea S. Vicari, Conall H. Watson, Sakoba Kéïta, Marie Paule Kieny*, John Arne Røttingen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

586 Citations (Scopus)

Abstract

Background A recombinant, replication-competent vesicular stomatitis virus-based vaccine expressing a surface glycoprotein of Zaire Ebolavirus (rVSV-ZEBOV) is a promising Ebola vaccine candidate. We report the results of an interim analysis of a trial of rVSV-ZEBOV in Guinea, west Africa. Methods For this open-label, cluster-randomised ring vaccination trial, suspected cases of Ebola virus disease in Basse-Guinée (Guinea, west Africa) were independently ascertained by Ebola response teams as part of a national surveillance system. After laboratory confirmation of a new case, clusters of all contacts and contacts of contacts were defined and randomly allocated 1:1 to immediate vaccination or delayed (21 days later) vaccination with rVSV-ZEBOV (one dose of 2×107 plaque-forming units, administered intramuscularly in the deltoid muscle). Adults (age ≥18 years) who were not pregnant or breastfeeding were eligible for vaccination. Block randomisation was used, with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 vs >20 individuals). The study is open label and masking of participants and field teams to the time of vaccination is not possible, but Ebola response teams and laboratory workers were unaware of allocation to immediate or delayed vaccination. Taking into account the incubation period of the virus of about 10 days, the prespecified primary outcome was laboratory-confirmed Ebola virus disease with onset of symptoms at least 10 days after randomisation. The primary analysis was per protocol and compared the incidence of Ebola virus disease in eligible and vaccinated individuals in immediate vaccination clusters with the incidence in eligible individuals in delayed vaccination clusters. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193. Findings Between April 1, 2015, and July 20, 2015, 90 clusters, with a total population of 7651 people were included in the planned interim analysis. 48 of these clusters (4123 people) were randomly assigned to immediate vaccination with rVSV-ZEBOV, and 42 clusters (3528 people) were randomly assigned to delayed vaccination with rVSV-ZEBOV. In the immediate vaccination group, there were no cases of Ebola virus disease with symptom onset at least 10 days after randomisation, whereas in the delayed vaccination group there were 16 cases of Ebola virus disease from seven clusters, showing a vaccine efficacy of 100% (95% CI 74·7-100·0; p=0·0036). No new cases of Ebola virus disease were diagnosed in vaccinees from the immediate or delayed groups from 6 days post-vaccination. At the cluster level, with the inclusion of all eligible adults, vaccine effectiveness was 75·1% (95% CI -7·1 to 94·2; p=0·1791), and 76·3% (95% CI -15·5 to 95·1; p=0·3351) with the inclusion of everyone (eligible or not eligible for vaccination). 43 serious adverse events were reported; one serious adverse event was judged to be causally related to vaccination (a febrile episode in a vaccinated participant, which resolved without sequelae). Assessment of serious adverse events is ongoing. Interpretation The results of this interim analysis indicate that rVSV-ZEBOV might be highly efficacious and safe in preventing Ebola virus disease, and is most likely effective at the population level when delivered during an Ebola virus disease outbreak via a ring vaccination strategy. Funding WHO, with support from the Wellcome Trust (UK); Médecins Sans Frontières; the Norwegian Ministry of Foreign Affairs through the Research Council of Norway; and the Canadian Government through the Public Health Agency of Canada, Canadian Institutes of Health Research, International Development Research Centre, and Department of Foreign Affairs, Trade and Development.

Original languageEnglish
Article number71
Pages (from-to)857-866
Number of pages10
JournalThe Lancet
Volume386
Issue number9996
DOIs
Publication statusPublished - 29 Aug 2015

Bibliographical note

Funding Information:
We thank the people in Basse-Guinée for their participation, and all the field, laboratory, and data management staff who worked extremely hard and under difficult conditions to successfully implement this study. Merck Sharp & Dohme provided the vaccine used in the trial. We would like to acknowledge the support of the following organisations: Wellcome Trust , UK Department of International Development , Guinean Ministry of Health , Norwegian Ministry of Foreign Affairs , US Department of Defense , Public Health Agency of Canada , Swiss Agency for Therapeutic Products , the Bill & Melinda Gates Foundation , Health Canada , and the European Commission . We also thank the following individuals who directly contributed to the study: Jeremy Farrar, D A Henderson, Richard Peto, David Hone, Tore Godal, Djilali Abdelghafour, Yap Boum, Mar Cabeza-Cabrerizo, Rokiatu Dembele, Ibrahima Diatta, Mamoudou Harouna Djingarey, Julia Djonova, Andres Garcia, Myriam Grubo, Pierre Gsell, Yper Hall, Raul Iraheta, Olivier Lapujade, Nicola Low, Murray Lumpkin, Thomas Mauget, Christine Maure, Corinne Merle, Nicholas Misso, Bjørg Dystvold Nilsson, Marie-Pierre Preziosi, Vasee Moorthy, Jean-Marie Okwo Bele, William Perea, Guenal Rodier, Martina Rothenbühler, Peter Smith, Samba Sow, Graciela Spizzamiglio, Milagritos Tapia, Guido Torelli, Sara Sofie Viksmoen Watle, and our colleagues at WHO for their support with implementation of the trial. We also thank all members of our scientific advisory group, our data and safety monitoring board, and the Guinea vaccine trial working group.

Funding Information:
ME, WJE, AC, and CHW have acted as unpaid advisors to WHO on Ebola vaccination and report travel and accommodation paid for by WHO to attend meetings. WJE is a co-investigator on the European Commission Innovative Medicines Initiative-funded EBOVAC trial of the Johnson & Johnson prime-boost Ebola vaccine candidate, for which he has received a grant from the European Commission Innovative Medicines Initiative , and his partner is an epidemiologist at GlaxoSmithKline, in a role unrelated to the company's development of an Ebola vaccine. AC and CHW have acted as unpaid advisors to the EBOVAC trial, for which CHW reports travel and accommodation paid for by the EBOVAC consortium to attend a meeting. AC has received non-financial support from Janssen outside the submitted work. SG has received grants from the European Commission during the conduct of the study. ST has received grants from Research Council of Norway , during the conduct of the study. The other authors declare no competing interests.

Publisher Copyright:
© 2015 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved.

Fingerprint

Dive into the research topics of 'Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial'. Together they form a unique fingerprint.

Cite this