Immune response of a two-dose heterologous Ebola vaccine regimen: summary of three African clinical trials using a single validated Filovirus Animal Nonclinical Group enzyme-linked immunosorbent assay in a single accredited laboratory

BACKGROUND: This analysis evaluated the immune response to the two-dose, heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola virus vaccine regimen, administered 56-days apart, from multiple African sites based on results from one analytic laboratory. METHODS: Immunogenicity across three trials (EBL2002, EBL2004/PREVAC, EBL3001) conducted in East and West Africa is summarised. Vaccine-induced Ebola glycoprotein-binding antibody concentrations were analysed by Q(2) Solutions laboratory at baseline, 21 days (EBL2002 and EBL3001) or 28 days (EBL2004) post-dose 2 (regimen completion), and 12 months post-dose 1 using the validated Filovirus Animal Nonclinical Group Ebola glycoprotein enzyme-linked immunosorbent assay (ELISA). Responders were defined as those with a >2.5-fold increase from baseline or the lower limit of quantification (LLOQ) if <LLOQ at baseline. FINDINGS: At 21 or 28 (21/28) days post-dose 2, the geometric mean concentration (GMC) range was 3810–7518 ELISA units (EU)/mL (percent responders: ≥98%) in adults, 9929–13532 EU/mL (≥98%) in adolescents aged 12–17 years, 10,212–17388 EU/mL (≥99%) in older children, and 22,568–25111 EU/mL (≥98%) in younger children. When stratified by country, GMCs at 21/28 days post-dose 2 were generally similar among adults and within paediatric cohorts (percent responders: 95%–100%). At month 12, GMC range was 259–437 EU/mL (percent responders: 49%–88%) in adults and 386–1139 EU/mL (70%–100%) in paediatric participants. INTERPRETATION: Based on data from a single laboratory using a single validated assay, Ad26.ZEBOV, MVA-BN-Filo induced a strong humoral immune response, with ≥95% of participants across countries classified as responders at 21/28 days post-dose 2 (regimen completion), regardless of age. FUNDING: Janssen Vaccines & Prevention BV; Innovative Medicines Initiative.