Abstract
IntroductionThe Ebola virus disease (EVD) outbreak in 2014–2016 in West Africa was the largest on record and provided an opportunity for large clinical trials and accelerated efforts to develop an effective and safe preventative vaccine. Multiple questions regarding the safety, immunogenicity, and efficacy of EVD vaccines remain unanswered. To address these gaps in the evidence base, the Partnership for Research on Ebola Vaccines (PREVAC) trial was designed. This paper describes the design, methods, and baseline results of the PREVAC trial and discusses challenges that led to different protocol amendments.MethodsThis is a randomized, double-blind, placebo-controlled phase 2 clinical trial of three vaccine strategies against the Ebola virus in healthy volunteers 1 year of age and above. The three vaccine strategies being studied are the rVSVΔG-ZEBOV-GP vaccine, with and without a booster dose at 56 days, and the Ad26.ZEBOV,MVA-FN-Filo vaccine regimen with Ad26.ZEBOV given as the first dose and the MVA-FN-Filo vaccination given 56 days later. There have been 4 versions of the protocol with those enrolled in Version 4.0 comprising the primary analysis cohort. The primary endpoint is based on the antibody titer against the Ebola virus surface glycoprotein measured 12 months following the final injection.ResultsFrom April 2017 to December 2018, a total of 5002 volunteers were screened and 4789 enrolled. Participants were enrolled at 6 sites in four countries (Guinea, Liberia, Sierra Leone, and Mali). Of the 4789 participants, 2560 (53%) were adults and 2229 (47%) were children. Those < 18 years of age included 549 (12%) aged 1 to 4 years, 750 (16%) 5 to 11 years, and 930 (19%) aged 12–17 years. At baseline, the median (25th, 75th percentile) antibody titer to Ebola virus glycoprotein for 1090 participants was 72 (50, 116) EU/mL.DiscussionThe PREVAC trial is evaluating—placebo-controlled—two promising Ebola candidate vaccines in advanced stages of development. The results will address unanswered questions related to short- and long-term safety and immunogenicity for three vaccine strategies in adults and children.Trial registrationClinicalTrials.gov NCT02876328. Registered on 23 August 2016.
Highlights
The Ebola virus disease (EVD) outbreak in 2014–2016 in West Africa was the largest on record and provided an opportunity for large clinical trials and accelerated efforts to develop an effective and safe preventative vaccine
There were no cases of Ebola virus disease 10 days or more following vaccination among 2108 contacts and contacts of contacts who were vaccinated immediately compared to 10 such cases in 1429 contacts and contacts of contacts who initially consented to receive vaccination 21 days after randomization [2]
Based upon these and other data this vaccine has been approved by the European Medicines Agency (EMA) and the U.S Food and Drug Administration (FDA) for the prevention of Ebola virus disease in individuals 18 years of age and older
Summary
The Ebola virus disease (EVD) outbreak in 2014–2016 in West Africa was the largest on record and provided an opportunity for large clinical trials and accelerated efforts to develop an effective and safe preventative vaccine. In that trial, which was conducted mainly in adults, no EVD events occurred more than 10 days after vaccination Based upon these and other data this vaccine has been approved by the European Medicines Agency (EMA) and the U.S Food and Drug Administration (FDA) for the prevention of Ebola virus disease in individuals 18 years of age and older. Tolerability, and immunogenicity from multiple studies supported the European marketing authorization for this Ebola twodose heterologous vaccine regimen granted by the European Commission after assessment by European Medical Agency in July 2020 for the prevention of Ebola virus disease caused by the Zaire ebolavirus species in individuals aged one year and above. The planned phase 3 component of PREVAIL I could not be completed because of the decline in cases of EVD resulting from public health efforts
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