PMID- 34714820
OWN - NLM
STAT- MEDLINE
DCOM- 20211214
LR  - 20211214
IS  - 1549-1676 (Electronic)
IS  - 1549-1277 (Print)
IS  - 1549-1277 (Linking)
VI  - 18
IP  - 10
DP  - 2021 Oct
TI  - Safety and immunogenicity of 2-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola 
      vaccination in healthy and HIV-infected adults: A randomised, placebo-controlled 
      Phase II clinical trial in Africa.
PG  - e1003813
LID - 10.1371/journal.pmed.1003813 [doi]
LID - e1003813
AB  - BACKGROUND: We investigated safety, tolerability, and immunogenicity of the 
      heterologous 2-dose Ebola vaccination regimen in healthy and HIV-infected adults 
      with different intervals between Ebola vaccinations. METHODS AND FINDINGS: In 
      this randomised, observer-blind, placebo-controlled Phase II trial, 668 healthy 
      18- to 70-year-olds and 142 HIV-infected 18- to 50-year-olds were enrolled from 1 
      site in Kenya and 2 sites each in Burkina Faso, Cote d'Ivoire, and Uganda. 
      Participants received intramuscular Ad26.ZEBOV followed by MVA-BN-Filo at 28-, 
      56-, or 84-day intervals, or saline. Females represented 31.4% of the healthy 
      adult cohort in contrast to 69.7% of the HIV-infected cohort. A subset of healthy 
      adults received booster vaccination with Ad26.ZEBOV or saline at Day 365. 
      Following vaccinations, adverse events (AEs) were collected until 42 days post 
      last vaccination and serious AEs (SAEs) were recorded from signing of the ICF 
      until the end of the study. The primary endpoint was safety, and the secondary 
      endpoint was immunogenicity. Anti-Ebola virus glycoprotein (EBOV GP) binding and 
      neutralising antibodies were measured at baseline and at predefined time points 
      throughout the study. The first participant was enrolled on 9 November 2015, and 
      the date of last participant's last visit was 12 February 2019. No 
      vaccine-related SAEs and mainly mild-to-moderate AEs were observed among the 
      participants. The most frequent solicited AEs were injection-site pain (local), 
      and fatigue, headache, and myalgia (systemic), respectively. Twenty-one days 
      post-MVA-BN-Filo vaccination, geometric mean concentrations (GMCs) with 95% 
      confidence intervals (CIs) of EBOV GP binding antibodies in healthy adults in 
      28-, 56-, and 84-day interval groups were 3,085 EU/mL (2,648 to 3,594), 7,518 
      EU/mL (6,468 to 8,740), and 7,300 EU/mL (5,116 to 10,417), respectively. In 
      HIV-infected adults in 28- and 56-day interval groups, GMCs were 4,207 EU/mL 
      (3,233 to 5,474) and 5,283 EU/mL (4,094 to 6,817), respectively. Antibody 
      responses were observed until Day 365. Ad26.ZEBOV booster vaccination after 1 
      year induced an anamnestic response. Study limitations include that some healthy 
      adult participants either did not receive dose 2 or received dose 2 outside of 
      their protocol-defined interval and that the follow-up period was limited to 365 
      days for most participants. CONCLUSIONS: Ad26.ZEBOV, MVA-BN-Filo vaccination was 
      well tolerated and immunogenic in healthy and HIV-infected African adults. 
      Increasing the interval between vaccinations from 28 to 56 days improved the 
      magnitude of humoral immune responses. Antibody levels persisted to at least 1 
      year, and Ad26.ZEBOV booster vaccination demonstrated the presence of 
      vaccination-induced immune memory. These data supported the approval by the 
      European Union for prophylaxis against EBOV disease in adults and children >/=1 
      year of age. TRIAL REGISTRATION: ClinicalTrials.gov NCT02564523.
FAU - Barry, Houreratou
AU  - Barry H
AUID- ORCID: 0000-0001-8114-1240
AD  - Centre MURAZ, Bobo-Dioulasso, Burkina Faso.
FAU - Mutua, Gaudensia
AU  - Mutua G
AD  - KAVI-Institute of Clinical Research University of Nairobi, Nairobi, Kenya.
FAU - Kibuuka, Hannah
AU  - Kibuuka H
AD  - Makerere University-Walter Reed Project, Kampala, Uganda.
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 - 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, Ouagadougou, Burkina Faso.
FAU - Meda, Nicolas
AU  - Meda N
AUID- ORCID: 0000-0003-2523-8747
AD  - Centre MURAZ, Bobo-Dioulasso, Burkina Faso.
FAU - Anzala, Omu
AU  - Anzala O
AUID- ORCID: 0000-0003-2892-7847
AD  - KAVI-Institute of Clinical Research University of Nairobi, Nairobi, Kenya.
FAU - Eholie, Serge
AU  - Eholie S
AD  - Unit of Infectious and Tropical Diseases, BPV3, Treichville University Teaching 
      Hospital, Abidjan, Cote d'Ivoire.
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, 
      F-33000, 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, 
      F-33000, 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
AU  - De Rosa S
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 - 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 - Douoguih, Macaya
AU  - Douoguih 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, 
      F-33000, Bordeaux, France.
AD  - Vaccine Research Institute (VRI), Creteil, France.
CN  - EBL2002 Study group
LA  - eng
SI  - ClinicalTrials.gov/NCT02564523
GR  - DH_/Department of Health/United Kingdom
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20211029
PL  - United States
TA  - PLoS Med
JT  - PLoS medicine
JID - 101231360
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Ebola Vaccines)
RN  - 0 (Glycoproteins)
RN  - 0 (Placebos)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - Adult
MH  - Antibodies, Neutralizing/immunology
MH  - Antibody Formation/immunology
MH  - Dose-Response Relationship, Immunologic
MH  - Ebola Vaccines/*adverse effects/*immunology
MH  - Female
MH  - Genetic Vectors/immunology
MH  - Glycoproteins/immunology
MH  - HIV Infections/*complications/*immunology
MH  - Humans
MH  - Immunity, Cellular/immunology
MH  - Male
MH  - Placebos
MH  - Vaccination/*adverse effects
MH  - Viral Proteins/immunology
PMC - PMC8555783
COIS- I have read the journal's policy and the authors of this manuscript have the 
      following competing interests: HB, CB, LR reports 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 and Prevention, during the conduct 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 declared ownership 
      of shares in Janssen, Pharmaceutical Companies of Johnson & Johnson. All other 
      authors have nothing to disclose.
EDAT- 2021/10/30 06:00
MHDA- 2021/12/15 06:00
PMCR- 2021/10/29
CRDT- 2021/10/29 17:15
PHST- 2021/01/13 00:00 [received]
PHST- 2021/09/13 00:00 [accepted]
PHST- 2021/10/29 17:15 [entrez]
PHST- 2021/10/30 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/10/29 00:00 [pmc-release]
AID - PMEDICINE-D-21-00186 [pii]
AID - 10.1371/journal.pmed.1003813 [doi]
PST - epublish
SO  - PLoS Med. 2021 Oct 29;18(10):e1003813. doi: 10.1371/journal.pmed.1003813. 
      eCollection 2021 Oct.