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 laboratoryResearch in context
Chelsea McLean,
Houreratou Barry,
Mark Kieh,
Zacchaeus Anywaine,
Baimba Tapima Rogers,
Seydou Doumbia,
Sodiomon B. Sirima,
Alimamy Serry-Bangura,
Abdoul Habib Beavogui,
Auguste Gaddah,
Michael Katwere,
Jenny Hendriks,
Babajide Keshinro,
Serge Eholie,
Hannah Kibuuka,
Stephen B. Kennedy,
Omu Anzala,
Mohamed Samai,
Eric D'Ortenzio,
Bailah Leigh,
Samba Sow,
Rodolphe Thiébaut,
Brian Greenwood,
Deborah Watson-Jones,
Macaya Douoguih,
Kerstin Luhn,
Cynthia Robinson
Affiliations
Chelsea McLean
Janssen Vaccines and Prevention BV, Leiden, the Netherlands; Corresponding author. Janssen Vaccines & Prevention BV, Archimedesweg 6, 2333 CN, Leiden, the Netherlands.
Houreratou Barry
Centre MURAZ, Bobo-Dioulasso, Burkina Faso
Mark Kieh
Partnership for Research on Ebola Virus in Liberia (PREVAIL), Monrovia, Liberia
Zacchaeus Anywaine
Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
Baimba Tapima Rogers
University of Sierra Leone, Freetown, Sierra Leone
Seydou Doumbia
University Clinical Research Center, University of Sciences, Technique and Technology of Bamako, Bamako, Mali
Sodiomon B. Sirima
Groupe de Recherche Action en Santé (GRAS), Ouagadougou, Burkina Faso
Alimamy Serry-Bangura
University of Sierra Leone, Freetown, Sierra Leone
Abdoul Habib Beavogui
Centre National de Formation et de Recherche en Santé Rurale de Mafèrinyah, Mafèrinyah, Guinea
Auguste Gaddah
Janssen Research and Development, Beerse, Belgium
Michael Katwere
Janssen Vaccines and Prevention BV, Leiden, the Netherlands
Jenny Hendriks
Janssen Vaccines and Prevention BV, Leiden, the Netherlands
Babajide Keshinro
Janssen Vaccines and Prevention BV, Leiden, the Netherlands
Serge Eholie
Medical School, University Felix Houphouet Boigny, Abidjan, Cote d'Ivoire
Hannah Kibuuka
Makerere University Walter Reed Project, Kampala, Uganda
Stephen B. Kennedy
Partnership for Research on Ebola Virus in Liberia (PREVAIL), Monrovia, Liberia
Omu Anzala
Kenya AIDS Vaccine Initiative (KAVI), University of Nairobi, Nairobi, Kenya
Mohamed Samai
University of Sierra Leone, Freetown, Sierra Leone
Eric D'Ortenzio
ANRS Emerging Infectious Diseases, Institut national de la santé et de la recherche médicale (Inserm), Paris, France
Bailah Leigh
University of Sierra Leone, Freetown, Sierra Leone
Samba Sow
Centre pour le Développement des Vaccins, Bamako, Mali
Rodolphe Thiébaut
University of Bordeaux, Inserm, Bordeaux Population Health Research Center, Bordeaux, France
Brian Greenwood
London School of Hygiene and Tropical Medicine, London, UK
Deborah Watson-Jones
London School of Hygiene and Tropical Medicine, London, UK; Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania
Macaya Douoguih
Janssen Vaccines and Prevention BV, Leiden, the Netherlands
Kerstin Luhn
Janssen Vaccines and Prevention BV, Leiden, the Netherlands
Cynthia Robinson
Janssen Vaccines and Prevention BV, Leiden, the Netherlands
Summary: 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 Q2 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 paediatricparticipants. 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.
