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.

<h4>Background</h4>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.<h4>Methods and findings</h4>In this randomised, observer-bl...

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Autores principales:	Houreratou Barry, Gaudensia Mutua, Hannah Kibuuka, Zacchaeus Anywaine, Sodiomon B Sirima, Nicolas Meda, Omu Anzala, Serge Eholie, Christine Bétard, Laura Richert, Christine Lacabaratz, M Juliana McElrath, Stephen De Rosa, Kristen W Cohen, Georgi Shukarev, Cynthia Robinson, Auguste Gaddah, Dirk Heerwegh, Viki Bockstal, Kerstin Luhn, Maarten Leyssen, Macaya Douoguih, Rodolphe Thiébaut, EBL2002 Study group
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/86e4c5b953964c10a11b39af7650a996
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spelling	oai:doaj.org-article:86e4c5b953964c10a11b39af7650a9962021-12-02T19:55:35ZSafety 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.1549-12771549-167610.1371/journal.pmed.1003813https://doaj.org/article/86e4c5b953964c10a11b39af7650a9962021-10-01T00:00:00Zhttps://doi.org/10.1371/journal.pmed.1003813https://doaj.org/toc/1549-1277https://doaj.org/toc/1549-1676<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.<h4>Trial registration</h4>ClinicalTrials.gov NCT02564523.Houreratou BarryGaudensia MutuaHannah KibuukaZacchaeus AnywaineSodiomon B SirimaNicolas MedaOmu AnzalaSerge EholieChristine BétardLaura RichertChristine LacabaratzM Juliana McElrathStephen De RosaKristen W CohenGeorgi ShukarevCynthia RobinsonAuguste GaddahDirk HeerweghViki BockstalKerstin LuhnMaarten LeyssenMacaya DouoguihRodolphe ThiébautEBL2002 Study groupPublic Library of Science (PLoS)articleMedicineRENPLoS Medicine, Vol 18, Iss 10, p e1003813 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Houreratou Barry Gaudensia Mutua Hannah Kibuuka Zacchaeus Anywaine Sodiomon B Sirima Nicolas Meda Omu Anzala Serge Eholie Christine Bétard Laura Richert Christine Lacabaratz M Juliana McElrath Stephen De Rosa Kristen W Cohen Georgi Shukarev Cynthia Robinson Auguste Gaddah Dirk Heerwegh Viki Bockstal Kerstin Luhn Maarten Leyssen Macaya Douoguih Rodolphe Thiébaut EBL2002 Study group 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.
description	<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.<h4>Trial registration</h4>ClinicalTrials.gov NCT02564523.
format	article
author	Houreratou Barry Gaudensia Mutua Hannah Kibuuka Zacchaeus Anywaine Sodiomon B Sirima Nicolas Meda Omu Anzala Serge Eholie Christine Bétard Laura Richert Christine Lacabaratz M Juliana McElrath Stephen De Rosa Kristen W Cohen Georgi Shukarev Cynthia Robinson Auguste Gaddah Dirk Heerwegh Viki Bockstal Kerstin Luhn Maarten Leyssen Macaya Douoguih Rodolphe Thiébaut EBL2002 Study group
author_facet	Houreratou Barry Gaudensia Mutua Hannah Kibuuka Zacchaeus Anywaine Sodiomon B Sirima Nicolas Meda Omu Anzala Serge Eholie Christine Bétard Laura Richert Christine Lacabaratz M Juliana McElrath Stephen De Rosa Kristen W Cohen Georgi Shukarev Cynthia Robinson Auguste Gaddah Dirk Heerwegh Viki Bockstal Kerstin Luhn Maarten Leyssen Macaya Douoguih Rodolphe Thiébaut EBL2002 Study group
author_sort	Houreratou Barry
title	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.
title_short	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.
title_full	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.
title_fullStr	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.
title_full_unstemmed	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.
title_sort	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.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/86e4c5b953964c10a11b39af7650a996
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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.

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