Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in infants: a phase 2, randomised, double-blind, active-controlled trial in Guinea and Sierra Leone
E Choi, Boris Lacarra, Muhammed O. Afolabi, Boni Maxime Ale, Frank Baiden, Christine Bétard, Julie Foster, Benjamin Hamzé, Christine Schwimmer, Daniela Manno, Éric D’Ortenzio, David Ishola, Cheick Mohamed Keita, Babajide Keshinro, Yusupha Njie, Wim van Dijck, Auguste Gaddah, Dickson Anumendem, Brett Lowe, Renaud Vatrinet, Bolarinde Lawal, Godfrey T Otieno, Mohamed Samai, Gibrilla F. Deen, Ibrahim Swaray, A Kamara, Michael Kamara, Mame Aminata Diagne, Dickens Kowuor, Chelsea McLean, Bailah Leigh, Abdoul Habib Béavogui, Maarten Leyssen, Kerstin Lühn, Cynthia Robinson, Macaya Douoguih, Brian Greenwood, Rodolphe Thiébaut, Deborah Watson‐Jones, Thomas A. Mooney, Lansana Conteh, M A Bangura, M A Bangura, H Jalloh, Ibrahim Franklyn Kamara, M Kamara, S Koroma, Mohamed Sesay, Mohamed Sesay, A T Deen, A Kamara, E L Kamara, SLM Kamara, Alusine H. Koroma, I S Mansaray, Massah Massaquoi, A Nabie, Dickens Kowuor, Yusupha Njie, Lazarus Odeny, Mahmud Sheku, Abdulai Jalloh, Amadou Sow, E Swaray, F Mansaray, T Sessie, J-HC Sunders, SI-S Turay, J Weekes, M Pessima, Alie Wurie, M Conteh, M I Jalloh, PBD Kamara, D P Kanneh, M Kanneh, I Komeh, Mohamed Koroma, M Kuyateh, F F Mansaray, Bailah Leigh, Deborah Watson‐Jones, Mohamed Samai, Gibrilla F. Deen, Tom Sesay, Peter Piot, Brian Greenwood, Shelley Lees, Heidi J. Larson, Muhammed O. Afolabi, David Ishola, Frank Baiden, Farba Faye, Daniel Tindanbil, Michael Kamara, Ibrahim Swaray, A Bangura, A M Kamara, Foday Morovia, J A Kallon
Abstract
BACKGROUND: This study assessed the safety and immunogenicity of the Ad26.ZEBOV and MVA-BN-Filo Ebola virus (EBOV) vaccine regimen in infants aged 4-11 months in Guinea and Sierra Leone. METHODS: In this phase 2, randomised, double-blind, active-controlled trial, we randomly assigned healthy infants (1:1 in a sentinel cohort, 5:2 for the remaining infants via an interactive web response system) to receive Ad26.ZEBOV followed by MVA-BN-Filo (Ebola vaccine group) or two doses of meningococcal quadrivalent conjugate vaccine (control group) administered 56 days apart. Infants were recruited at two sites in west Africa: Conakry, Guinea, and Kambia, Sierra Leone. All infants received the meningococcal vaccine 8 months after being randomly assigned. The primary objective was safety. The secondary objective was immunogenicity, measured as EBOV glycoprotein-binding antibody concentration 21 days post-dose 2, using the Filovirus Animal Non-Clinical Group ELISA. This study is registered with ClinicalTrials.gov (NCT03929757) and the Pan African Clinical Trials Registry (PACTR201905827924069). FINDINGS: From Aug 20 to Nov 29, 2019, 142 infants were screened and 108 were randomly assigned (Ebola vaccine n=75; control n=33). The most common solicited local adverse event was injection-site pain (Ebola vaccine 15 [20%] of 75; control four [12%] of 33). The most common solicited systemic adverse events with the Ebola vaccine were irritability (26 [35%] of 75), decreased appetite (18 [24%] of 75), pyrexia (16 [21%] of 75), and decreased activity (15 [20%] of 75). In the control group, ten (30%) of 33 had irritability, seven (21%) of 33 had decreased appetite, three (9%) of 33 had pyrexia, and five (15%) of 33 had decreased activity. The frequency of unsolicited adverse events was 83% (62 of 75 infants) in the Ebola vaccine group and 85% (28 of 33 infants) in the control group. No serious adverse events were vaccine-related. In the Ebola vaccine group, EBOV glycoprotein-binding antibody geometric mean concentrations (GMCs) at 21 days post-dose 2 were 27 700 ELISA units (EU)/mL (95% CI 20 477-37 470) in infants aged 4-8 months and 20 481 EU/mL (15 325-27 372) in infants aged 9-11 months. The responder rate was 100% (74 of 74 responded). In the control group, GMCs for both age groups were less than the lower limit of quantification and the responder rate was 3% (one of 33 responded). INTERPRETATION: Ad26.ZEBOV and MVA-BN-Filo was well tolerated and induced strong humoral responses in infants younger than 1 year. There were no safety concerns related to vaccination. FUNDING: Janssen Vaccines & Prevention and Innovative Medicines Initiative 2 Joint Undertaking. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.