دورية أكاديمية
Tolerability and immunogenicity of an intranasally-administered adenovirus-vectored COVID-19 vaccine: An open-label partially-randomised ascending dose phase I trial.
العنوان: | Tolerability and immunogenicity of an intranasally-administered adenovirus-vectored COVID-19 vaccine: An open-label partially-randomised ascending dose phase I trial. |
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المؤلفون: | Madhavan M; Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK; Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK., Ritchie AJ; Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK., Aboagye J; Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK., Jenkin D; Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK; Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK., Provstgaad-Morys S; Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK., Tarbet I; Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK., Woods D; Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK., Davies S; Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK., Baker M; Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK., Platt A; Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK., Flaxman A; Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK., Smith H; Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK., Belij-Rammerstorfer S; Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK., Wilkins D; Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, 1 Medimmune Way, Gaithersburg, MD 20878, USA., Kelly EJ; Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, 1 Medimmune Way, Gaithersburg, MD 20878, USA., Villafana T; Clinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA., Green JA; Clinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK., Poulton I; Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK., Lambe T; Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK; Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK; China Academy of Medical Sciences Oxford Institute, University of Oxford, NDM Research Building, Old Road Campus, Headington, Oxford OX3 7FZ, UK., Hill AVS; Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK., Ewer KJ; Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK., Douglas AD; Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK. Electronic address: sandy.douglas@ndm.ox.ac.uk. |
المصدر: | EBioMedicine [EBioMedicine] 2022 Nov; Vol. 85, pp. 104298. Date of Electronic Publication: 2022 Oct 10. |
نوع المنشور: | Clinical Trial, Phase I; Journal Article; Randomized Controlled Trial |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier B.V Country of Publication: Netherlands NLM ID: 101647039 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2352-3964 (Electronic) Linking ISSN: 23523964 NLM ISO Abbreviation: EBioMedicine Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [Amsterdam] : Elsevier B.V., [2014]- |
مواضيع طبية MeSH: | COVID-19*/prevention & control , Viral Vaccines*, Adult ; Humans ; Adenoviridae/genetics ; Antibodies, Viral ; BNT162 Vaccine ; ChAdOx1 nCoV-19 ; COVID-19 Vaccines/adverse effects ; SARS-CoV-2 ; Vaccination/adverse effects ; mRNA Vaccines |
مستخلص: | Background: Intranasal vaccination may induce protective local and systemic immune responses against respiratory pathogens. A number of intranasal SARS-CoV-2 vaccine candidates have achieved protection in pre-clinical challenge models, including ChAdOx1 nCoV-19 (AZD1222, University of Oxford / AstraZeneca). Methods: We performed a single-centre open-label Phase I clinical trial of intranasal vaccination with ChAdOx1 nCoV-19 in healthy adults, using the existing formulation produced for intramuscular administration. Thirty SARS-CoV-2 vaccine-naïve participants were allocated to receive 5 × 10 9 viral particles (VP, n=6), 2 × 10 10 VP (n=12), or 5 × 10 10 VP (n=12). Fourteen received second intranasal doses 28 days later. A further 12 received non-study intramuscular mRNA SARS-CoV-2 vaccination between study days 22 and 46. To investigate intranasal ChAdOx1 nCoV-19 as a booster, six participants who had previously received two intramuscular doses of ChAdOx1 nCoV-19 and six who had received two intramuscular doses of BNT162b2 (Pfizer / BioNTech) were given a single intranasal dose of 5 × 10 10 VP of ChAdOx1 nCoV-19. Objectives were to assess safety (primary) and mucosal antibody responses (secondary). Findings: Reactogenicity was mild or moderate. Antigen-specific mucosal antibody responses to intranasal vaccination were detectable in a minority of participants, rarely exceeding levels seen after SARS-CoV-2 infection. Systemic responses to intranasal vaccination were typically weaker than after intramuscular vaccination with ChAdOx1 nCoV-19. Antigen-specific mucosal antibody was detectable in participants who received an intramuscular mRNA vaccine after intranasal vaccination. Seven participants developed symptomatic SARS-CoV-2 infection. Interpretation: This formulation of intranasal ChAdOx1 nCoV-19 showed an acceptable tolerability profile but induced neither a consistent mucosal antibody response nor a strong systemic response. Funding: AstraZeneca. Competing Interests: Declaration of interests Oxford University has entered into a partnership with AstraZeneca to develop ChAdOx1 nCoV-19. AJR and KE may receive royalties arising from the University of Oxford/AstraZeneca COVID-19 vaccine. TL is named as an inventor on a patent application covering this SARS-CoV-2 vaccine and was previously a consultant to Vaccitech on an unrelated project. AVSH is a cofounder of and former consultant to Vaccitech is named as an inventor on a patent covering design and use of ChAdOx1-vectored vaccines (PCT/GB2012/000467), and may receive royalties arising for the University of Oxford/AstraZeneca COVID-19 vaccine. DW, EJK, TV, and JAG are current employees of AstraZeneca and hold or may hold AstraZeneca stock. ADD reports grants and personal fees from AstraZeneca outside of the submitted work, is a named inventor on patent applications relating the chimpanzee adenovirus platform technology and manufacturing, and may receive royalties arising from the University of Oxford/AstraZeneca COVID-19 vaccine. All other authors declare no competing interests. (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.) |
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فهرسة مساهمة: | Keywords: Adenovirus vector; Intranasal vaccination; Mucosal antibody; SARS-CoV-2 |
المشرفين على المادة: | 0 (Antibodies, Viral) 0 (BNT162 Vaccine) B5S3K2V0G8 (ChAdOx1 nCoV-19) 0 (COVID-19 Vaccines) 0 (Viral Vaccines) |
تواريخ الأحداث: | Date Created: 20221013 Date Completed: 20221118 Latest Revision: 20231213 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC9550199 |
DOI: | 10.1016/j.ebiom.2022.104298 |
PMID: | 36229342 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2352-3964 |
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DOI: | 10.1016/j.ebiom.2022.104298 |