During the 2018–2020 Ebola virus disease outbreak in Democratic Republic of the Congo, a phase 3 trial of the Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine (DRC-EB-001) commenced in Goma, with participants being offered the two-dose regimen given 56 days apart. Suspension of trial activities in 2020 due to the COVID-19 pandemic led to some participants receiving a late dose 2 outside the planned interval. Blood samples were collected from adults, adolescents, and children prior to their delayed dose 2 vaccination and 21 days after, and tested for IgG binding antibodies against Ebola virus glycoprotein using the Filovirus Animal Nonclinical Group (FANG) ELISA. Results from 133 participants showed a median two-dose interval of 9.3 months. The pre-dose 2 antibody geometric mean concentration (GMC) was 217 ELISA Units (EU)/mL (95% CI 157; 301) in adults, 378 EU/mL (281; 510) in adolescents, and 558 EU/mL (471; 661) in children. At 21 days post-dose 2, the GMC increased to 22,194 EU/mL (16,726; 29,449) in adults, 37,896 EU/mL (29,985; 47,893) in adolescents, and 34,652 EU/mL (27,906; 43,028) in children. Participants receiving a delayed dose 2 had a higher GMC at 21 days post-dose 2 than those who received a standard 56-day regimen in other African trials, but similar to those who received the regimen with an extended interval.
Ebola virus disease (EVD) continues to be a significant public health problem in sub-Saharan Africa, especially in the Democratic Republic of the Congo (DRC). Large-scale vaccination during outbreaks may reduce virus transmission. We established a large population-based clinical trial of a heterologous, two-dose prophylactic vaccine during an outbreak in eastern DRC to determine vaccine effectiveness.
METHODS AND ANALYSIS
This open-label, non-randomised, population-based trial enrolled eligible adults and children aged 1 year and above. Participants were offered the two-dose candidate EVD vaccine regimen VAC52150 (Ad26.ZEBOV, Modified Vaccinia Ankara (MVA)-BN-Filo), with the doses being given 56 days apart. After vaccination, serious adverse events (SAEs) were passively recorded until 1 month post dose 2. 1000 safety subset participants were telephoned at 1 month post dose 2 to collect SAEs. 500 pregnancy subset participants were contacted to collect SAEs at D7 and D21 post dose 1 and at D7, 1 month, 3 months and 6 months post dose 2, unless delivery was before these time points. The first 100 infants born to these women were given a clinical examination 3 months post delivery. Due to COVID-19 and temporary suspension of dose 2 vaccinations, at least 50 paediatric and 50 adult participants were enrolled into an immunogenicity subset to examine immune responses following a delayed second dose. Samples collected predose 2 and at 21 days post dose 2 will be tested using the Ebola viruses glycoprotein Filovirus Animal Non-Clinical Group ELISA. For qualitative research, in-depth interviews and focus group discussions were being conducted with participants or parents/care providers of paediatric participants.
ETHICS AND DISSEMINATION
Approved by Comité National d'Ethique et de la Santé du Ministère de la santé de RDC, Comité d'Ethique de l'Ecole de Santé Publique de l'Université de Kinshasa, the LSHTM Ethics Committee and the MSF Ethics Review Board. Findings will be presented to stakeholders and conferences. Study data will be made available for open access.
TRIAL REGISTRATION NUMBER
NCT04152486.