PMID- 35015777
OWN - NLM
STAT- MEDLINE
DCOM- 20220210
LR  - 20220210
IS  - 1549-1676 (Electronic)
IS  - 1549-1277 (Print)
IS  - 1549-1277 (Linking)
VI  - 19
IP  - 1
DP  - 2022 Jan
TI  - 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.
PG  - e1003865
LID - 10.1371/journal.pmed.1003865 [doi]
LID - e1003865
AB  - 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 x 1010 viral particles) 
      and MVA-BN-Filo (1 x 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.
FAU - Anywaine, Zacchaeus
AU  - Anywaine Z
AUID- ORCID: 0000-0001-5771-5515
AD  - Medical Research Council/Uganda Virus Research Institute and London School of 
      Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
FAU - Barry, Houreratou
AU  - Barry H
AUID- ORCID: 0000-0001-8114-1240
AD  - Centre MURAZ, Bobo-Dioulasso, Burkina Faso.
FAU - Anzala, Omu
AU  - Anzala O
AD  - KAVI - Institute of Clinical Research University of Nairobi, Nairobi, Kenya.
FAU - Mutua, Gaudensia
AU  - Mutua G
AD  - KAVI - Institute of Clinical Research University of Nairobi, Nairobi, Kenya.
FAU - Sirima, Sodiomon B
AU  - Sirima SB
AUID- ORCID: 0000-0002-0972-4211
AD  - Centre National de Recherche et de Formation sur le Paludisme (CNRFP), Unite de 
      Recherche Clinique de Banfora, Banfora, Burkina Faso.
FAU - Eholie, Serge
AU  - Eholie S
AD  - Unit of Infectious and Tropical Diseases, BPV3, Treichville University Teaching 
      Hospital, Abidjan, Cote d'Ivoire.
FAU - Kibuuka, Hannah
AU  - Kibuuka H
AD  - Makerere University - Walter Reed Project, Kampala, Uganda.
FAU - Betard, Christine
AU  - Betard C
AD  - 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.
FAU - Richert, Laura
AU  - Richert L
AUID- ORCID: 0000-0002-7682-2225
AD  - 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.
AD  - Vaccine Research Institute (VRI), Creteil, France.
FAU - Lacabaratz, Christine
AU  - Lacabaratz C
AUID- ORCID: 0000-0001-6925-0225
AD  - Vaccine Research Institute (VRI), Creteil, France.
AD  - Universite Paris-Est Creteil, Faculte de Medecine, INSERM U955, Team 16, Creteil, 
      France.
FAU - McElrath, M Juliana
AU  - McElrath MJ
AUID- ORCID: 0000-0003-2276-7117
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, United States of America.
FAU - De Rosa, Stephen C
AU  - De Rosa SC
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, United States of America.
FAU - Cohen, Kristen W
AU  - Cohen KW
AUID- ORCID: 0000-0002-8901-9941
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, United States of America.
FAU - Shukarev, Georgi
AU  - Shukarev G
AUID- ORCID: 0000-0001-5154-7047
AD  - Janssen Vaccines and Prevention, Leiden, the Netherlands.
FAU - Katwere, Michael
AU  - Katwere M
AUID- ORCID: 0000-0001-7917-289X
AD  - Janssen Vaccines and Prevention, Leiden, the Netherlands.
FAU - Robinson, Cynthia
AU  - Robinson C
AUID- ORCID: 0000-0002-0219-4123
AD  - Janssen Vaccines and Prevention, Leiden, the Netherlands.
FAU - Gaddah, Auguste
AU  - Gaddah A
AD  - Janssen Research & Development, Beerse, Belgium.
FAU - Heerwegh, Dirk
AU  - Heerwegh D
AD  - Janssen Research & Development, Beerse, Belgium.
FAU - Bockstal, Viki
AU  - Bockstal V
AD  - Janssen Vaccines and Prevention, Leiden, the Netherlands.
FAU - Luhn, Kerstin
AU  - Luhn K
AD  - Janssen Vaccines and Prevention, Leiden, the Netherlands.
FAU - Leyssen, Maarten
AU  - Leyssen M
AD  - Janssen Vaccines and Prevention, Leiden, the Netherlands.
FAU - Thiebaut, Rodolphe
AU  - Thiebaut R
AUID- ORCID: 0000-0002-5235-3962
AD  - 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.
AD  - Vaccine Research Institute (VRI), Creteil, France.
FAU - Douoguih, Macaya
AU  - Douoguih M
AD  - Janssen Vaccines and Prevention, Leiden, the Netherlands.
CN  - EBL2002 Study group
LA  - eng
SI  - ClinicalTrials.gov/NCT02564523
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20220111
PL  - United States
TA  - PLoS Med
JT  - PLoS medicine
JID - 101231360
RN  - 0 (Ebola Vaccines)
SB  - IM
MH  - Adolescent
MH  - Africa, Eastern
MH  - Africa, Western
MH  - Child
MH  - Child, Preschool
MH  - Ebola Vaccines/*adverse effects
MH  - Ebolavirus/*immunology
MH  - Female
MH  - Hemorrhagic Fever, Ebola/*prevention & control
MH  - Humans
MH  - *Immunity, Humoral
MH  - *Immunogenicity, Vaccine
MH  - Injections, Intramuscular
MH  - Male
PMC - PMC8752100
COIS- I have read the journal's policy and the authors of this manuscript have the 
      following competing interests: ZA, HB, CB, LR, CL and RT report grants from 
      IMI2-2 [Grant Agreement EBOVAC2 (No.115861) from the Innovative Medicines 
      Initiative 2 Joint Undertaking which receives support from the European Union's 
      Horizon 2020 research and innovation programme] during the conduct of the study. 
      SBS reports grants from Janssen Vaccines & Prevention B.V. during the conduct of 
      the study. MK was a full-time employee of Janssen, Pharmaceutical Companies of 
      Johnson & Johnson at the time of the study. GS, CR, AG, DH, VB, KL, ML and MD 
      were full-time employees of Janssen, Pharmaceutical Companies of Johnson & 
      Johnson at the time of the study, and may own shares in Janssen, Pharmaceutical 
      Companies of Johnson & Johnson. All other authors have nothing to disclose.
EDAT- 2022/01/12 06:00
MHDA- 2022/02/11 06:00
PMCR- 2022/01/11
CRDT- 2022/01/11 17:37
PHST- 2021/05/20 00:00 [received]
PHST- 2021/11/09 00:00 [accepted]
PHST- 2022/01/11 17:37 [entrez]
PHST- 2022/01/12 06:00 [pubmed]
PHST- 2022/02/11 06:00 [medline]
PHST- 2022/01/11 00:00 [pmc-release]
AID - PMEDICINE-D-21-02242 [pii]
AID - 10.1371/journal.pmed.1003865 [doi]
PST - epublish
SO  - PLoS Med. 2022 Jan 11;19(1):e1003865. doi: 10.1371/journal.pmed.1003865. 
      eCollection 2022 Jan.