Safety and Immunogenicity of Malaria Vectored Vaccines Given with Routine Expanded Program on Immunization Vaccines in Gambian Infants and Neonates: A Randomized Controlled Trial
BackgroundHeterologous prime-boost vaccination with chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) encoding multiple epitope string thrombospondin-related adhesion protein (ME-TRAP) has shown acceptable safety and promising immunogenicity in African adult and pediatric po...
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Frontiers Media S.A.
2017-11-01
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Series: | Frontiers in Immunology |
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Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01551/full |
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Article |
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language |
English |
format |
Article |
sources |
DOAJ |
author |
Victorine A. Mensah Sophie Roetynck Ebrima K. Kanteh Georgina Bowyer Amy Ndaw Francis Oko Carly M. Bliss Ya Jankey Jagne Riccardo Cortese Alfredo Nicosia Alfredo Nicosia Alfredo Nicosia Rachel Roberts Flavia D’Alessio Odile Leroy Babacar Faye Beate Kampmann Beate Kampmann Badara Cisse Kalifa Bojang Stephen Gerry Nicola K. Viebig Alison M. Lawrie Ed Clarke Egeruan B. Imoukhuede Katie J. Ewer Adrian V. S. Hill Adrian V. S. Hill Muhammed O. Afolabi |
spellingShingle |
Victorine A. Mensah Sophie Roetynck Ebrima K. Kanteh Georgina Bowyer Amy Ndaw Francis Oko Carly M. Bliss Ya Jankey Jagne Riccardo Cortese Alfredo Nicosia Alfredo Nicosia Alfredo Nicosia Rachel Roberts Flavia D’Alessio Odile Leroy Babacar Faye Beate Kampmann Beate Kampmann Badara Cisse Kalifa Bojang Stephen Gerry Nicola K. Viebig Alison M. Lawrie Ed Clarke Egeruan B. Imoukhuede Katie J. Ewer Adrian V. S. Hill Adrian V. S. Hill Muhammed O. Afolabi Safety and Immunogenicity of Malaria Vectored Vaccines Given with Routine Expanded Program on Immunization Vaccines in Gambian Infants and Neonates: A Randomized Controlled Trial Frontiers in Immunology vaccines clinical trials malaria cellular immune response cytokines |
author_facet |
Victorine A. Mensah Sophie Roetynck Ebrima K. Kanteh Georgina Bowyer Amy Ndaw Francis Oko Carly M. Bliss Ya Jankey Jagne Riccardo Cortese Alfredo Nicosia Alfredo Nicosia Alfredo Nicosia Rachel Roberts Flavia D’Alessio Odile Leroy Babacar Faye Beate Kampmann Beate Kampmann Badara Cisse Kalifa Bojang Stephen Gerry Nicola K. Viebig Alison M. Lawrie Ed Clarke Egeruan B. Imoukhuede Katie J. Ewer Adrian V. S. Hill Adrian V. S. Hill Muhammed O. Afolabi |
author_sort |
Victorine A. Mensah |
title |
Safety and Immunogenicity of Malaria Vectored Vaccines Given with Routine Expanded Program on Immunization Vaccines in Gambian Infants and Neonates: A Randomized Controlled Trial |
title_short |
Safety and Immunogenicity of Malaria Vectored Vaccines Given with Routine Expanded Program on Immunization Vaccines in Gambian Infants and Neonates: A Randomized Controlled Trial |
title_full |
Safety and Immunogenicity of Malaria Vectored Vaccines Given with Routine Expanded Program on Immunization Vaccines in Gambian Infants and Neonates: A Randomized Controlled Trial |
title_fullStr |
Safety and Immunogenicity of Malaria Vectored Vaccines Given with Routine Expanded Program on Immunization Vaccines in Gambian Infants and Neonates: A Randomized Controlled Trial |
title_full_unstemmed |
Safety and Immunogenicity of Malaria Vectored Vaccines Given with Routine Expanded Program on Immunization Vaccines in Gambian Infants and Neonates: A Randomized Controlled Trial |
title_sort |
safety and immunogenicity of malaria vectored vaccines given with routine expanded program on immunization vaccines in gambian infants and neonates: a randomized controlled trial |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2017-11-01 |
description |
BackgroundHeterologous prime-boost vaccination with chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) encoding multiple epitope string thrombospondin-related adhesion protein (ME-TRAP) has shown acceptable safety and promising immunogenicity in African adult and pediatric populations. If licensed, this vaccine could be given to infants receiving routine childhood immunizations. We therefore evaluated responses to ChAd63 MVA ME-TRAP when co-administered with routine Expanded Program on Immunization (EPI) vaccines.MethodsWe enrolled 65 Gambian infants and neonates, aged 16, 8, or 1 week at first vaccination and randomized them to receive either ME-TRAP and EPI vaccines or EPI vaccines only. Safety was assessed by the description of vaccine-related adverse events (AEs). Immunogenicity was evaluated using IFNγ enzyme-linked immunospot, whole-blood flow cytometry, and anti-TRAP IgG ELISA. Serology was performed to confirm all infants achieved protective titers to EPI vaccines.ResultsThe vaccines were well tolerated in all age groups with no vaccine-related serious AEs. High-level TRAP-specific IgG and T cell responses were generated after boosting with MVA. CD8+ T cell responses, previously found to correlate with protection, were induced in all groups. Antibody responses to EPI vaccines were not altered significantly.ConclusionMalaria vectored prime-boost vaccines co-administered with routine childhood immunizations were well tolerated. Potent humoral and cellular immunity induced by ChAd63 MVA ME-TRAP did not reduce the immunogenicity of co-administered EPI vaccines, supporting further evaluation of this regimen in infant populations.Clinical Trial RegistrationThe clinical trial was registered on http://Clinicaltrials.gov (NCT02083887) and the Pan-African Clinical Trials Registry (PACTR201402000749217). |
topic |
vaccines clinical trials malaria cellular immune response cytokines |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2017.01551/full |
work_keys_str_mv |
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doaj-ec79be823a6948b69302a94bf68cd4c92020-11-25T00:55:04ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-11-01810.3389/fimmu.2017.01551306375Safety and Immunogenicity of Malaria Vectored Vaccines Given with Routine Expanded Program on Immunization Vaccines in Gambian Infants and Neonates: A Randomized Controlled TrialVictorine A. Mensah0Sophie Roetynck1Ebrima K. Kanteh2Georgina Bowyer3Amy Ndaw4Francis Oko5Carly M. Bliss6Ya Jankey Jagne7Riccardo Cortese8Alfredo Nicosia9Alfredo Nicosia10Alfredo Nicosia11Rachel Roberts12Flavia D’Alessio13Odile Leroy14Babacar Faye15Beate Kampmann16Beate Kampmann17Badara Cisse18Kalifa Bojang19Stephen Gerry20Nicola K. Viebig21Alison M. Lawrie22Ed Clarke23Egeruan B. Imoukhuede24Katie J. Ewer25Adrian V. S. Hill26Adrian V. S. Hill27Muhammed O. Afolabi28Université Cheikh Anta Diop, Dakar, SenegalMedical Research Council Unit, Fajara, GambiaMedical Research Council Unit, Fajara, GambiaThe Jenner Institute Laboratories, University of Oxford, Oxford, United KingdomUniversité Cheikh Anta Diop, Dakar, SenegalMedical Research Council Unit, Fajara, GambiaThe Jenner Institute Laboratories, University of Oxford, Oxford, United KingdomMedical Research Council Unit, Fajara, GambiaKeires AG, Basel, SwitzerlandReiThera, Rome, ItalyCEINGE, Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, University Federico II, Naples, ItalyCentre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, Churchill Hospital, Oxford, United KingdomEuropean Vaccine Initiative, UniversitätsKlinikum Heidelberg, Heidelberg, GermanyEuropean Vaccine Initiative, UniversitätsKlinikum Heidelberg, Heidelberg, GermanyUniversité Cheikh Anta Diop, Dakar, SenegalMedical Research Council Unit, Fajara, Gambia0Centre for International Child Health, Imperial College London, London, United KingdomUniversité Cheikh Anta Diop, Dakar, SenegalMedical Research Council Unit, Fajara, Gambia1Centre for Statistics in Medicine, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United KingdomEuropean Vaccine Initiative, UniversitätsKlinikum Heidelberg, Heidelberg, GermanyCentre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, Churchill Hospital, Oxford, United KingdomMedical Research Council Unit, Fajara, GambiaCentre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, Churchill Hospital, Oxford, United KingdomThe Jenner Institute Laboratories, University of Oxford, Oxford, United KingdomThe Jenner Institute Laboratories, University of Oxford, Oxford, United KingdomCentre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, Churchill Hospital, Oxford, United KingdomMedical Research Council Unit, Fajara, GambiaBackgroundHeterologous prime-boost vaccination with chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) encoding multiple epitope string thrombospondin-related adhesion protein (ME-TRAP) has shown acceptable safety and promising immunogenicity in African adult and pediatric populations. If licensed, this vaccine could be given to infants receiving routine childhood immunizations. We therefore evaluated responses to ChAd63 MVA ME-TRAP when co-administered with routine Expanded Program on Immunization (EPI) vaccines.MethodsWe enrolled 65 Gambian infants and neonates, aged 16, 8, or 1 week at first vaccination and randomized them to receive either ME-TRAP and EPI vaccines or EPI vaccines only. Safety was assessed by the description of vaccine-related adverse events (AEs). Immunogenicity was evaluated using IFNγ enzyme-linked immunospot, whole-blood flow cytometry, and anti-TRAP IgG ELISA. Serology was performed to confirm all infants achieved protective titers to EPI vaccines.ResultsThe vaccines were well tolerated in all age groups with no vaccine-related serious AEs. High-level TRAP-specific IgG and T cell responses were generated after boosting with MVA. CD8+ T cell responses, previously found to correlate with protection, were induced in all groups. Antibody responses to EPI vaccines were not altered significantly.ConclusionMalaria vectored prime-boost vaccines co-administered with routine childhood immunizations were well tolerated. Potent humoral and cellular immunity induced by ChAd63 MVA ME-TRAP did not reduce the immunogenicity of co-administered EPI vaccines, supporting further evaluation of this regimen in infant populations.Clinical Trial RegistrationThe clinical trial was registered on http://Clinicaltrials.gov (NCT02083887) and the Pan-African Clinical Trials Registry (PACTR201402000749217).http://journal.frontiersin.org/article/10.3389/fimmu.2017.01551/fullvaccinesclinical trialsmalariacellular immune responsecytokines |