Ring vaccination with rVSV-ZEBOV under expanded access in response to an outbreak of Ebola virus disease in Guinea, 2016: an operational and vaccine safety report.

BACKGROUND: In March, 2016, a flare-up of Ebola virus disease was reported in Guinea, and in response ring vaccination with the unlicensed rVSV-ZEBOV vaccine was introduced under expanded access, the first time that an Ebola vaccine has been used in an outbreak setting outside a clinical trial. Here we describe the safety of rVSV-ZEBOV candidate vaccine and operational feasibility of ring vaccination as a reactive strategy in a resource-limited rural setting. METHODS: Approval for expanded access and compassionate use was rapidly sought and obtained from relevant authorities. Vaccination teams and frozen vaccine were flown to the outbreak settings. Rings of contacts and contacts of contacts were defined and eligible individuals, who had given informed consent, were vaccinated and followed up for 21 days under good clinical practice conditions. FINDINGS: Between March 17 and April 21, 2016, 1510 individuals were vaccinated in four rings in Guinea, including 303 individuals aged between 6 years and 17 years and 307 front-line workers. It took 10 days to vaccinate the first participant following the confirmation of the first case of Ebola virus disease. No secondary cases of Ebola virus disease occurred among the vaccinees. Adverse events following vaccination were reported in 47 (17%) 6-17 year olds (all mild) and 412 (36%) adults (individuals older than 18 years; 98% were mild). Children reported fewer arthralgia events than adults (one [<1%] of 303 children vs 81 [7%] of 1207 adults). No severe vaccine-related adverse events were reported. INTERPRETATION: The results show that a ring vaccination strategy can be rapidly and safely implemented at scale in response to Ebola virus disease outbreaks in rural settings. FUNDING: WHO, Gavi, and the World Food Programme

Partnership for Research on Ebola VACcination (PREVAC): protocol of a randomized, double-blind, placebo-controlled phase 2 clinical trial evaluating three vaccine strategies against Ebola in healthy volunteers in four West African countries

International audienceAbstract Introduction 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. 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. Methods This 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. Results From 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. Discussion The 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 registration ClinicalTrials.gov NCT02876328 . Registered on 23 August 2016