دورية أكاديمية
أعرض في EDS

First field efficacy trial of the ChAd63 MVA ME-TRAP vectored malaria vaccine candidate in 5-17 months old infants and children.

التفاصيل البيبلوغرافية
العنوان: First field efficacy trial of the ChAd63 MVA ME-TRAP vectored malaria vaccine candidate in 5-17 months old infants and children.
المؤلفون: Tiono AB; Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso., Nébié I; Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso., Anagnostou N; The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom., Coulibaly AS; Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso., Bowyer G; The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom., Lam E; The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom., Bougouma EC; Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso., Ouedraogo A; Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso., Yaro JBB; Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso., Barry A; Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso., Roberts R; The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom., Rampling T; The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom., Bliss C; The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom., Hodgson S; The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom., Lawrie A; The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom., Ouedraogo A; Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso., Imoukhuede EB; The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom., Ewer KJ; The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom., Viebig NK; European Vaccine Initiative, Universitäts Klinikum Heidelberg, Heidelberg, Germany., Diarra A; Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso., Leroy O; European Vaccine Initiative, Universitäts Klinikum Heidelberg, Heidelberg, Germany., Bejon P; Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya., Hill AVS; The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom., Sirima SB; Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso.; Groupe de Recherche Action en Santé (GRAS), Ouagadougou, Burkina Faso.
المصدر: PloS one [PLoS One] 2018 Dec 12; Vol. 13 (12), pp. e0208328. Date of Electronic Publication: 2018 Dec 12 (Print Publication: 2018).
نوع المنشور: Clinical Trial, Phase II; Journal Article; Randomized Controlled Trial
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Malaria Vaccines/*therapeutic use, Adenoviruses, Simian/genetics ; Double-Blind Method ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Infant ; Kaplan-Meier Estimate ; Kenya ; Leukocytes, Mononuclear/immunology ; Malaria/immunology ; Malaria/prevention & control ; Male ; Plasmodium falciparum/immunology ; Plasmodium falciparum/pathogenicity ; T-Lymphocytes/metabolism ; Vaccinia virus/genetics
مستخلص: Background: Heterologous prime boost immunization with chimpanzee adenovirus 63 (ChAd63) and Modified Vaccinia Virus Ankara (MVA) vectored vaccines is a strategy previously shown to provide substantial protective efficacy against P. falciparum infection in United Kingdom adult Phase IIa sporozoite challenge studies (approximately 20-25% sterile protection with similar numbers showing clear delay in time to patency), and greater point efficacy in a trial in Kenyan adults.
Methodology: We conducted the first Phase IIb clinical trial assessing the safety, immunogenicity and efficacy of ChAd63 MVA ME-TRAP in 700 healthy malaria exposed children aged 5-17 months in a highly endemic malaria transmission area of Burkina Faso.
Results: ChAd63 MVA ME-TRAP was shown to be safe and immunogenic but induced only moderate T cell responses (median 326 SFU/106 PBMC (95% CI 290-387)) many fold lower than in previous trials. No significant efficacy was observed against clinical malaria during the follow up period, with efficacy against the primary endpoint estimate by proportional analysis being 13.8% (95%CI -42.4 to 47.9) at sixth month post MVA ME-TRAP and 3.1% (95%CI -15.0 to 18.3; p = 0.72) by Cox regression.
Conclusions: This study has confirmed ChAd63 MVA ME-TRAP is a safe and immunogenic vaccine regimen in children and infants with prior exposure to malaria. But no significant protective efficacy was observed in this very highly malaria-endemic setting.
Trial Registration: ClinicalTrials.gov NCT01635647. Pactr.org PACTR201208000404131.
Competing Interests: AVSH is a named inventor on patent applications and issued patents relating to malaria vectored vaccines and immunization regimes. This does not alter the author’s adherence to all the PLOS ONE policies on sharing data and materials.
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سلسلة جزيئية: ClinicalTrials.gov NCT01635647
المشرفين على المادة: 0 (Malaria Vaccines)
تواريخ الأحداث: Date Created: 20181213 Date Completed: 20190506 Latest Revision: 20200309
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC6291132
DOI: 10.1371/journal.pone.0208328
PMID: 30540808
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0208328