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
Chelsea McLean, Houreratou Barry, Mark Kieh, Zacchaeus Anywaine, Baimba Rogers, Seydou Doumbia, Sodiomon B. Sirima, Alimamy Serry-Bangura, Abdoul Habib Béavogui, Auguste Gaddah, Michael Katwere, Jenny Hendriks, Babajide Keshinro, Serge Eholié, Hannah Kibuuka, Stephen B. Kennedy, Omu Anzala, Mohamed Samai, Éric D’Ortenzio, Bailah Leigh, Samba O. Sow, Rodolphe Thiébaut, Brian Greenwood, Deborah Watson‐Jones, Macaya Douoguih, Kerstin Lühn, Cynthia Robinson
Abstract
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: 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.