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
<h4>Background</h4> 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 vacc...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS Medicine |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8752100/?tool=EBI |
| _version_ | 1819003847766441984 |
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| author | Zacchaeus Anywaine Houreratou Barry Omu Anzala Gaudensia Mutua Sodiomon B. Sirima Serge Eholie Hannah Kibuuka Christine Bétard Laura Richert Christine Lacabaratz M. Juliana McElrath Stephen C. De Rosa Kristen W. Cohen Georgi Shukarev Michael Katwere Cynthia Robinson Auguste Gaddah Dirk Heerwegh Viki Bockstal Kerstin Luhn Maarten Leyssen Rodolphe Thiébaut Macaya Douoguih on behalf of the EBL2002 Study group |
| author_facet | Zacchaeus Anywaine Houreratou Barry Omu Anzala Gaudensia Mutua Sodiomon B. Sirima Serge Eholie Hannah Kibuuka Christine Bétard Laura Richert Christine Lacabaratz M. Juliana McElrath Stephen C. De Rosa Kristen W. Cohen Georgi Shukarev Michael Katwere Cynthia Robinson Auguste Gaddah Dirk Heerwegh Viki Bockstal Kerstin Luhn Maarten Leyssen Rodolphe Thiébaut Macaya Douoguih on behalf of the EBL2002 Study group |
| author_sort | Zacchaeus Anywaine |
| collection | DOAJ |
| description | <h4>Background</h4> 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. <h4>Methods and findings</h4> 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. <h4>Conclusions</h4> 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. <h4>Trial registration</h4> ClinicalTrials.govNCT02564523. Zacchaeus Anywaine and co-workers study safety and immunogenicity of an Ebola vaccine among children and adolescents across four African countries. Author summary <h4>Why was the study done?</h4> There have been larger and more extensive Ebola virus disease (EVD) outbreaks in Africa in the past decade with no licenced treatments available. As such, there is an unmet medical need for prophylactic Ebola vaccines. This study was performed to evaluate whether a 2-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccination was safe and immunogenic in healthy African children. <h4>What did the researchers do and find?</h4> In this randomised, placebo-controlled, Phase II clinical trial, the Ad26.ZEBOV, MVA-BN-Filo Ebola vaccination regimen was administered to African participants in 2 age cohorts (12 to 17 and 4 to 11 years). No vaccine-related serious adverse events were reported, and robust immune responses were induced in both adolescents and children after receiving the active 2-dose regimen. <h4>What do these findings mean?</h4> These data support the use of the Ad26.ZEBOV, MVA-BN-Filo vaccination regimen in African adolescents and children at risk of Ebola infection. Although vaccination according to a 28-day regimen may lead to protection against EVD in a shorter time frame, vaccination according to a 56-day regimen results in higher EBOV GP binding and neutralising antibody responses. The observation that Ad26 preexisting immunity in the majority of participants does not affect the EBOV GP-specific antibody responses postvaccination augurs well for the use of this vaccine regimen even in regions with a high prevalence of preexisting Ad26 seropositivity. |
| first_indexed | 2024-12-20T23:27:31Z |
| format | Article |
| id | doaj.art-e1f49a02b0c94e9ba66ed470427070ec |
| institution | Directory Open Access Journal |
| issn | 1549-1277 1549-1676 |
| language | English |
| last_indexed | 2024-12-20T23:27:31Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Medicine |
| spelling | doaj.art-e1f49a02b0c94e9ba66ed470427070ec2022-12-21T19:23:21ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762022-01-01191Safety 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 trialZacchaeus AnywaineHoureratou BarryOmu AnzalaGaudensia MutuaSodiomon B. SirimaSerge EholieHannah KibuukaChristine BétardLaura RichertChristine LacabaratzM. Juliana McElrathStephen C. De RosaKristen W. CohenGeorgi ShukarevMichael KatwereCynthia RobinsonAuguste GaddahDirk HeerweghViki BockstalKerstin LuhnMaarten LeyssenRodolphe ThiébautMacaya Douoguihon behalf of the EBL2002 Study group<h4>Background</h4> 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. <h4>Methods and findings</h4> 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. <h4>Conclusions</h4> 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. <h4>Trial registration</h4> ClinicalTrials.govNCT02564523. Zacchaeus Anywaine and co-workers study safety and immunogenicity of an Ebola vaccine among children and adolescents across four African countries. Author summary <h4>Why was the study done?</h4> There have been larger and more extensive Ebola virus disease (EVD) outbreaks in Africa in the past decade with no licenced treatments available. As such, there is an unmet medical need for prophylactic Ebola vaccines. This study was performed to evaluate whether a 2-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccination was safe and immunogenic in healthy African children. <h4>What did the researchers do and find?</h4> In this randomised, placebo-controlled, Phase II clinical trial, the Ad26.ZEBOV, MVA-BN-Filo Ebola vaccination regimen was administered to African participants in 2 age cohorts (12 to 17 and 4 to 11 years). No vaccine-related serious adverse events were reported, and robust immune responses were induced in both adolescents and children after receiving the active 2-dose regimen. <h4>What do these findings mean?</h4> These data support the use of the Ad26.ZEBOV, MVA-BN-Filo vaccination regimen in African adolescents and children at risk of Ebola infection. Although vaccination according to a 28-day regimen may lead to protection against EVD in a shorter time frame, vaccination according to a 56-day regimen results in higher EBOV GP binding and neutralising antibody responses. The observation that Ad26 preexisting immunity in the majority of participants does not affect the EBOV GP-specific antibody responses postvaccination augurs well for the use of this vaccine regimen even in regions with a high prevalence of preexisting Ad26 seropositivity.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8752100/?tool=EBI |
| spellingShingle | Zacchaeus Anywaine Houreratou Barry Omu Anzala Gaudensia Mutua Sodiomon B. Sirima Serge Eholie Hannah Kibuuka Christine Bétard Laura Richert Christine Lacabaratz M. Juliana McElrath Stephen C. De Rosa Kristen W. Cohen Georgi Shukarev Michael Katwere Cynthia Robinson Auguste Gaddah Dirk Heerwegh Viki Bockstal Kerstin Luhn Maarten Leyssen Rodolphe Thiébaut Macaya Douoguih on behalf of the EBL2002 Study group 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 PLoS Medicine |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8752100/?tool=EBI |
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