Efficacy and Effectiveness of an rVSV-Vectored Vaccine
Expressing Ebola Surface Glycoprotein: Interim Results from
the Guinea Ring Vaccination Cluster-Randomised Trial
By Ana Maria Henao-Restrepo, Ira M Longini, Matthias Egger, Natalie E Dean, W John Edmunds, Anton Camacho, Miles W 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 Norheim, Ximena Riveros, Aboubacar Soumah, Sven Trelle, Andrea S Vicari, Conall H Watson, Sakoba Kéïta, Marie Paule Kieny*, John-Arne Røttingen*
July 31, 2015
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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.
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.
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.
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.
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.
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