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Clinical Trial
. 2023 May:91:104562.
doi: 10.1016/j.ebiom.2023.104562. Epub 2023 Apr 24.

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  1 , Houreratou Barry  2 , Mark Kieh  3 , Zacchaeus Anywaine  4 , Baimba Tapima Rogers  5 , Seydou Doumbia  6 , Sodiomon B Sirima  7 , Alimamy Serry-Bangura  5 , Abdoul Habib Beavogui  8 , Auguste Gaddah  9 , Michael Katwere  10 , Jenny Hendriks  10 , Babajide Keshinro  10 , Serge Eholie  11 , Hannah Kibuuka  12 , Stephen B Kennedy  3 , Omu Anzala  13 , Mohamed Samai  5 , Eric D'Ortenzio  14 , Bailah Leigh  5 , Samba Sow  15 , Rodolphe Thiébaut  16 , Brian Greenwood  17 , Deborah Watson-Jones  18 , Macaya Douoguih  10 , Kerstin Luhn  10 , Cynthia Robinson  10
Affiliations
Clinical Trial

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 et al. EBioMedicine. 2023 May.

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: 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 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.

Keywords: Ad26.ZEBOV; Africa; Ebola; MVA-BN-Filo; Vaccine.

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Conflict of interest statement

Declaration of interests CM, AG, JH, BK, MD, KL, and CR were full-time employees of Janssen Pharmaceuticals at the time of the study and report stock or stock options in Janssen Pharmaceuticals. HB's institution has received funding from the Innovative Medicines Initiative to conduct the EBL2002 study. M Katwere was a full-time employee of Janssen Pharmaceuticals at the time of the study. SE's institution has received funding from Inserm France to conduct the EBL2002 study. BL's institution has received funding from the Innovative Medicines Initiative to conduct the EBL3005 study. DW-J is a consortia partner with Janssen Pharmaceuticals on EBOVAC1 and EBOVAC3 projects, has received Ad26.MVA Ebola vaccines donated by Janssen Pharmaceuticals for clinical trials under EBOVAC1 and EBOVAC3 projects, and her institution has received funding from the Innovative Medicines Initiative to conduct the EBL3005 study. M Kieh, ZA, BTR, SD, SBS, AS-B, AHB, HK, SBK, OA, MS, EDO, SS, RT, and BG declare no competing interests.

Figures

Fig. 1
Fig. 1
Flow diagram for (a) adult and (b) paediatric participants in the EBL2004 study included in the analysis. Flow diagrams showing the derivation of samples from participants in the EBL2004 study included in the current analysis with immunogenicity assessments performed by Q2 Solutions. ∗This number includes an additional 11 participants who were selected for the Ad26.ZEBOV, MVA-BN-Filo regimen after unblinding due to missing month 12 samples for some randomly selected participants.
Fig. 2
Fig. 2
EBOV GP-binding antibody GMCs in adult participants at 21 or 28 days post-dose 2, stratified by country. EBOV GP-binding antibody GMCs at 21 or 28 days post-dose 2 are presented overall for adults who received the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen in EBL2002 (n = 136), HIV-infected adults in EBL2002 (n = 59), adults in EBL2004 (n = 236), and adults in EBL 3001 stage 1 (n = 42) and stage 2 (n = 182), as well as by country in each study. Samples were analysed according to Q2 Solution's FANG ELISA standard operating procedure, and a single reportable value for each participant sample at each timepoint was uploaded for statistical analysis. Error bars represent 95% CIs. CI; Confidence interval. EBOV GP; Ebola virus glycoprotein. ELISA; Enzyme-linked immunosorbent assay. EU; ELISA unit. FANG; Filovirus Animal Nonclinical Group. GMC; Geometric mean concentration. ∗N is the number of participants with data at baseline and at 21 days (EBL2002/EBL3001) or 28 days (EBL2004) post-dose 2.
Fig. 3
Fig. 3
EBOV-GP binding antibody GMCs in (a) adolescents, (b) older children, and (c) younger children at 21 or 28 days post-dose 2, stratified by country. EBOV GP-binding antibody GMCs at 21 or 28 days post-dose 2 are presented overall for paediatric participants who received the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen, including adolescents aged 12–17 years in EBL2002 (n = 53), EBL2004 (n = 125), and EBL3001 stage 2 (n = 134); older children aged 4–11 years in EBL2002 (n = 53) and EBL3001 stage 2 (n = 124) and 5–11 years in EBL2004 (n = 105); and younger children aged 1–4 years EBL2004 (n = 108) and 1–3 years in EBL3001 stage 2 (n = 124). GMCs are also shown by country for each study. Samples were analysed according to Q2 Solution's FANG ELISA standard operating procedure, and a single reportable value for each participant sample at each timepoint was uploaded for statistical analysis. Error bars represent 95% CIs. CI; Confidence interval. EBOV GP; Ebola virus glycoprotein. ELISA; Enzyme-linked immunosorbent assay. EU; ELISA unit. FANG; Filovirus Animal Nonclinical Group. GMC; Geometric mean concentration. ∗N is the number of participants with data at baseline and at 21 days (EBL2002/EBL3001) or 28 days (EBL2004) post-dose 2.
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References

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