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.

Autor:	Choi EM; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK. Electronic address: edward.choi@lshtm.ac.uk., Lacarra B; REACTing Unit, Inserm, Paris, France., Afolabi MO; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK; EBOVAC-Salone Project, Kambia, Sierra Leone., Ale BM; Clinical Investigation Center-Clinical Epidemiology, University of Bordeaux, Inserm, Institut Bergonié, EUCLID/F-CRIN CIC-EC1401, Bordeaux, France., Baiden F; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK; EBOVAC-Salone Project, Kambia, Sierra Leone., Bétard C; Clinical Investigation Center-Clinical Epidemiology, University of Bordeaux, Inserm, Institut Bergonié, EUCLID/F-CRIN CIC-EC1401, Bordeaux, France., Foster J; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK., Hamzé B; Pôle Recherche Clinique, Inserm, Paris, France., Schwimmer C; Clinical Investigation Center-Clinical Epidemiology, University of Bordeaux, Inserm, Institut Bergonié, EUCLID/F-CRIN CIC-EC1401, Bordeaux, France; Department of Medical Information, Centre Hospitalier Universitaire (CHU) de Bordeaux, EUCLID/F-CRIN CIC-EC1401, Inserm, Institut Bergonié, Bordeaux, France., Manno D; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK., D'Ortenzio E; ANRS, Maladies infectieuses émergentes, Inserm, Paris, France., Ishola D; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK; EBOVAC-Salone Project, Kambia, Sierra Leone., Keita CM; Centre National de Formation et de Recherche en Santé Rurale de Mafèrinyah, Forécariah, Guinea., Keshinro B; Janssen Vaccines & Prevention, Leiden, Netherlands., Njie Y; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK; EBOVAC-Salone Project, Kambia, Sierra Leone., van Dijck W; Janssen Research & Development, Beerse, Belgium., Gaddah A; Janssen Research & Development, Beerse, Belgium., Anumendem D; Janssen Research & Development, Beerse, Belgium., Lowe B; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK., Vatrinet R; REACTing Unit, Inserm, Paris, France., Lawal BJ; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK; EBOVAC-Salone Project, Kambia, Sierra Leone., Otieno GT; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK; EBOVAC-Salone Project, Kambia, Sierra Leone., Samai M; College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone., Deen GF; College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone., Swaray IB; College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone., Kamara AB; College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone., Kamara MM; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK., Diagne MA; Laboratoire de Sociologie, Anthropologie et Psychologie Sociale, Department of Sociology, Université Cheikh Anta Diop de Dakar, Dakar, Senegal., Kowuor D; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK., McLean C; Janssen Vaccines & Prevention, Leiden, Netherlands., Leigh B; College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone., Beavogui AH; Centre National de Formation et de Recherche en Santé Rurale de Mafèrinyah, Forécariah, Guinea., Leyssen M; Janssen Vaccines & Prevention, Leiden, Netherlands., Luhn K; Janssen Vaccines & Prevention, Leiden, Netherlands., Robinson C; Janssen Vaccines & Prevention, Leiden, Netherlands., Douoguih M; Janssen Vaccines & Prevention, Leiden, Netherlands., Greenwood B; Department of Disease Control, London School of Hygiene & Tropical Medicine, London, UK., Thiébaut R; Clinical Investigation Center-Clinical Epidemiology, University of Bordeaux, Inserm, Institut Bergonié, EUCLID/F-CRIN CIC-EC1401, Bordeaux, France; Department of Medical Information, Centre Hospitalier Universitaire (CHU) de Bordeaux, EUCLID/F-CRIN CIC-EC1401, Inserm, Institut Bergonié, Bordeaux, France., Watson-Jones D; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK; Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania.
Jazyk:	angličtina
Zdroj:	The Lancet. Global health [Lancet Glob Health] 2023 Nov; Vol. 11 (11), pp. e1743-e1752.
DOI:	10.1016/S2214-109X(23)00410-2
Abstrakt:	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. Competing Interests: Declaration of interests Janssen Vaccines & Prevention was the vaccine manufacturer and donated the vaccine for this study. BK, WvD, AG, DA, CM, ML, KL, CR, and MD were full-time employees of Janssen Pharmaceuticals at the time of the study and hold stock or stock options in Janssen Pharmaceuticals. All other authors declare funding from the Innovative Medicines Initiative 2 Joint Undertaking. (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu