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Safety and immunogenicity of 2-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccination in children and adolescents in Africa: A randomised, placebo-controlled, multicentre Phase II clinical trial.
Anywaine, Zacchaeus; Barry, Houreratou; Anzala, Omu; Mutua, Gaudensia; Sirima, Sodiomon B; Eholie, Serge; Kibuuka, Hannah; Bétard, Christine; Richert, Laura; Lacabaratz, Christine; McElrath, M Juliana; De Rosa, Stephen C; Cohen, Kristen W; Shukarev, Georgi; Katwere, Michael; Robinson, Cynthia; Gaddah, Auguste; Heerwegh, Dirk; Bockstal, Viki; Luhn, Kerstin; Leyssen, Maarten; Thiébaut, Rodolphe; Douoguih, Macaya.
Afiliação
  • Anywaine Z; Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
  • Barry H; Centre MURAZ, Bobo-Dioulasso, Burkina Faso.
  • Anzala O; KAVI - Institute of Clinical Research University of Nairobi, Nairobi, Kenya.
  • Mutua G; KAVI - Institute of Clinical Research University of Nairobi, Nairobi, Kenya.
  • Sirima SB; Centre National de Recherche et de Formation sur le Paludisme (CNRFP), Unité de Recherche Clinique de Banfora, Banfora, Burkina Faso.
  • Eholie S; Unit of Infectious and Tropical Diseases, BPV3, Treichville University Teaching Hospital, Abidjan, Côte d'Ivoire.
  • Kibuuka H; Makerere University - Walter Reed Project, Kampala, Uganda.
  • Bétard C; Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219; Inria SISTM team; CHU Bordeaux; CIC 1401, EUCLID/F-CRIN Clinical Trials Platform, Bordeaux, France.
  • Richert L; Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219; Inria SISTM team; CHU Bordeaux; CIC 1401, EUCLID/F-CRIN Clinical Trials Platform, Bordeaux, France.
  • Lacabaratz C; Vaccine Research Institute (VRI), Créteil, France.
  • McElrath MJ; Vaccine Research Institute (VRI), Créteil, France.
  • De Rosa SC; Université Paris-Est Créteil, Faculté de Médecine, INSERM U955, Team 16, Créteil, France.
  • Cohen KW; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
  • Shukarev G; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
  • Katwere M; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
  • Robinson C; Janssen Vaccines and Prevention, Leiden, the Netherlands.
  • Gaddah A; Janssen Vaccines and Prevention, Leiden, the Netherlands.
  • Heerwegh D; Janssen Vaccines and Prevention, Leiden, the Netherlands.
  • Bockstal V; Janssen Research & Development, Beerse, Belgium.
  • Luhn K; Janssen Research & Development, Beerse, Belgium.
  • Leyssen M; Janssen Vaccines and Prevention, Leiden, the Netherlands.
  • Thiébaut R; Janssen Vaccines and Prevention, Leiden, the Netherlands.
  • Douoguih M; Janssen Vaccines and Prevention, Leiden, the Netherlands.
PLoS Med ; 19(1): e1003865, 2022 01.
Article em En | MEDLINE | ID: mdl-35015777
BACKGROUND: Reoccurring Ebola outbreaks in West and Central Africa have led to serious illness and death in thousands of adults and children. The objective of this study was to assess safety, tolerability, and immunogenicity of the heterologous 2-dose Ad26.ZEBOV, MVA-BN-Filo vaccination regimen in adolescents and children in Africa. METHODS AND FINDINGS: In this multicentre, randomised, observer-blind, placebo-controlled Phase II study, 131 adolescents (12 to 17 years old) and 132 children (4 to 11 years old) were enrolled from Eastern and Western Africa and randomised 5:1 to receive study vaccines or placebo. Vaccine groups received intramuscular injections of Ad26.ZEBOV (5 × 1010 viral particles) and MVA-BN-Filo (1 × 108 infectious units) 28 or 56 days apart; placebo recipients received saline. Primary outcomes were safety and tolerability. Solicited adverse events (AEs) were recorded until 7 days after each vaccination and serious AEs (SAEs) throughout the study. Secondary and exploratory outcomes were humoral immune responses (binding and neutralising Ebola virus [EBOV] glycoprotein [GP]-specific antibodies), up to 1 year after the first dose. Enrolment began on February 26, 2016, and the date of last participant last visit was November 28, 2018. Of the 263 participants enrolled, 217 (109 adolescents, 108 children) received the 2-dose regimen, and 43 (20 adolescents, 23 children) received 2 placebo doses. Median age was 14.0 (range 11 to 17) and 7.0 (range 4 to 11) years for adolescents and children, respectively. Fifty-four percent of the adolescents and 51% of the children were male. All participants were Africans, and, although there was a slight male preponderance overall, the groups were well balanced. No vaccine-related SAEs were reported; solicited AEs were mostly mild/moderate. Twenty-one days post-MVA-BN-Filo vaccination, binding antibody responses against EBOV GP were observed in 100% of vaccinees (106 adolescents, 104 children). Geometric mean concentrations tended to be higher after the 56-day interval (adolescents 13,532 ELISA units [EU]/mL, children 17,388 EU/mL) than the 28-day interval (adolescents 6,993 EU/mL, children 8,007 EU/mL). Humoral responses persisted at least up to Day 365. A limitation of the study is that the follow-up period was limited to 365 days for the majority of the participants, and so it was not possible to determine whether immune responses persisted beyond this time period. Additionally, formal statistical comparisons were not preplanned but were only performed post hoc. CONCLUSIONS: The heterologous 2-dose vaccination was well tolerated in African adolescents and children with no vaccine-related SAEs. All vaccinees displayed anti-EBOV GP antibodies after the 2-dose regimen, with higher responses in the 56-day interval groups. The frequency of pyrexia after vaccine or placebo was higher in children than in adolescents. These data supported the prophylactic indication against EBOV disease in a paediatric population, as licenced in the EU. TRIAL REGISTRATION: ClinicalTrials.gov NCT02564523.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença pelo Vírus Ebola / Vacinas contra Ebola / Ebolavirus / Imunidade Humoral / Imunogenicidade da Vacina Tipo de estudo: Clinical_trials Limite: Adolescent / Child / Child, preschool / Female / Humans / Male País/Região como assunto: Africa Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença pelo Vírus Ebola / Vacinas contra Ebola / Ebolavirus / Imunidade Humoral / Imunogenicidade da Vacina Tipo de estudo: Clinical_trials Limite: Adolescent / Child / Child, preschool / Female / Humans / Male País/Região como assunto: Africa Idioma: En Ano de publicação: 2022 Tipo de documento: Article