International Journal of Infectious Diseases
Volume 53, Supplement, p1-176 – December 2016
International Meeting on Emerging Diseases and Surveillance (IMED) 2016 Abstracts
Highlights from the 6th International Meeting on Emerging Diseases and Surveillance (IMED 2016) Vienna, Austria from Nov 3 to 7, 2016
Britta Lassmann, Lawrence C. Madoff
Vaccine trials during outbreaks: The Sierra Leone trial to introduce a vaccine against Ebola (STRIVE) experience
Published in issue: December 2016
West Africa’s Ebola epidemic was unprecedented in size and complexity. In September 2014, exponential increase in cases raised concern that timely control might not be achievable without a vaccine, so vaccine development was accelerated. By late 2014, Phase 1 studies of candidate vaccines started, and multiple organizations began planning phase 2/3 studies with collaborators in Ebola-affected countries. The US Centers for Disease Control and Prevention sponsored STRIVE, a phase 2/3 trial in Sierra Leone, in collaboration with the College of Medicine and Allied Health Sciences, University of Sierra Leone, and the Ministry of Health and Sanitation. STRIVE was designed as an individually randomized trial to simultaneously evaluate safety and efficacy of recombinant vesicular stomatitis virus Zaire Ebola vaccine (rVSV-ZEBOV) in healthcare and frontline Ebola response workers; no placebo was used. Participants were randomized to immediate (within 7 days) or delayed (within 18-24 weeks) vaccination and followed for 6 months after vaccination for serious adverse events and Ebola infection. Sub-studies collected detailed safety, reactogenicity, and immunogenicity data. STRIVE established 7 enrollment and vaccination sites in 5 districts, 3 data centers, and a -80o C vaccine cold chain. STRIVE staff conducted >100 outreach sessions targeting potential participants, community members, and health leaders and trained >350 Sierra Leone staff. The study design evolved in response to the changing epidemiologic situation. A stepped wedge design (sequential vaccination after full enrollment) was initially considered but was replaced by phased enrollment to allow earlier vaccination in the context of the ongoing outbreak. After another trial demonstrated likely efficacy, some participants in the delayed vaccination group were vaccinated before 18-24 weeks. From April to December 2015, >8,650 participants were enrolled and >8,000 vaccinated. Ebola response measures successfully interrupted transmission, so vaccine efficacy could not be assessed. Preliminary analysis of safety data indicates no vaccine-related deaths or other serious adverse events; these data will be critical to application for licensure. Implementing STRIVE without detracting from the response to an epidemic of a highly lethal virus, in the face of limited infrastructure, high community concern, and changing epidemiology required extensive partnership-building, creativity, collaboration, and flexibility.