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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

dc.rights.licenseopenen_US
dc.contributor.authorANYWAINE, Zacchaeus
dc.contributor.authorBARRY, Houreratou
dc.contributor.authorANZALA, Omu
dc.contributor.authorMUTUA, Gaudensia
dc.contributor.authorSIRIMA, Sodiomon B.
dc.contributor.authorEHOLIE, Serge Paul
dc.contributor.authorKIBUUKA, Hannah
hal.structure.identifierStatistics In System biology and Translational Medicine [SISTM]
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorBETARD, Christine
hal.structure.identifierStatistics In System biology and Translational Medicine [SISTM]
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorRICHERT, Laura
dc.contributor.authorLACABARATZ, Christine
dc.contributor.authorMCELRATH, M. Juliana
dc.contributor.authorROSA, Stephen C. De
dc.contributor.authorCOHEN, Kristen W.
dc.contributor.authorSHUKAREV, Georgi
dc.contributor.authorKATWERE, Michael
dc.contributor.authorROBINSON, Cynthia
dc.contributor.authorGADDAH, Auguste
dc.contributor.authorHEERWEGH, Dirk
dc.contributor.authorBOCKSTAL, Viki
dc.contributor.authorLUHN, Kerstin
dc.contributor.authorLEYSSEN, Maarten
hal.structure.identifierStatistics In System biology and Translational Medicine [SISTM]
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTHIEBAUT, Rodolphe
dc.contributor.authorDOUOGUIH, Macaya
dc.date.accessioned2023-03-13T14:48:45Z
dc.date.available2023-03-13T14:48:45Z
dc.date.issued2022-01-11
dc.identifier.issn1549-1676en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/172275
dc.description.abstractEnBackground 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.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subject.enAdolescents
dc.subject.enAdverse events
dc.subject.enAntibodies
dc.subject.enAntibody response
dc.subject.enEnzyme-linked immunoassays
dc.subject.enImmune response
dc.subject.enVaccination and immunization
dc.subject.enVaccines
dc.title.enSafety 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
dc.typeArticle de revueen_US
dc.identifier.doi10.1371/journal.pmed.1003865en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed35015777en_US
bordeaux.journalPLoS Medicineen_US
bordeaux.volume19en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue1en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamSISTM_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.exportfalse
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=PLoS%20Medicine&rft.date=2022-01-11&rft.volume=19&rft.issue=1&rft.eissn=1549-1676&rft.issn=1549-1676&rft.au=ANYWAINE,%20Zacchaeus&BARRY,%20Houreratou&ANZALA,%20Omu&MUTUA,%20Gaudensia&SIRIMA,%20Sodiomon%20B.&rft.genre=article


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