دورية أكاديمية
أعرض في EDS

Tolerability and immunogenicity of an intranasally-administered adenovirus-vectored COVID-19 vaccine: An open-label partially-randomised ascending dose phase I trial.

التفاصيل البيبلوغرافية
العنوان: Tolerability and immunogenicity of an intranasally-administered adenovirus-vectored COVID-19 vaccine: An open-label partially-randomised ascending dose phase I trial.
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.)
References: Sci Transl Med. 2021 Aug 18;13(607):. (PMID: 34315826)
Sci Transl Med. 2021 Jan 20;13(577):. (PMID: 33288662)
Nat Commun. 2022 Sep 1;13(1):5135. (PMID: 36050304)
J Immunol. 2004 Aug 1;173(3):1978-86. (PMID: 15265932)
Lancet Infect Dis. 2021 Dec;21(12):1654-1664. (PMID: 34324836)
Virology. 2015 Aug;482:60-6. (PMID: 25827529)
Nat Rev Immunol. 2022 Apr;22(4):236-250. (PMID: 34312520)
Clin Vaccine Immunol. 2015 Dec 09;23(3):243-5. (PMID: 26656116)
Mucosal Immunol. 2022 Mar;15(3):379-388. (PMID: 34671115)
J Virol. 1987 Jun;61(6):1851-4. (PMID: 3553614)
Front Immunol. 2013 Aug 06;4:222. (PMID: 23964273)
J Infect Dis. 2015 Dec 1;212(11):1719-25. (PMID: 25977264)
Nature. 2020 Oct;586(7830):578-582. (PMID: 32731258)
Lancet. 2021 Jan 9;397(10269):99-111. (PMID: 33306989)
Vaccine. 2005 Jan 11;23(8):1029-36. (PMID: 15620476)
Lancet. 2020 Aug 15;396(10249):467-478. (PMID: 32702298)
J Vis Exp. 2018 Jan 21;(131):. (PMID: 29443104)
J Immunol. 2002 Mar 15;168(6):2930-8. (PMID: 11884464)
Vaccine. 1990 Oct;8(5):479-85. (PMID: 2251874)
Nat Commun. 2021 Nov 26;12(1):6871. (PMID: 34836955)
Vaccine. 2002 Jan 31;20(9-10):1340-53. (PMID: 11818152)
Sci Transl Med. 2021 Jan 20;13(577):. (PMID: 33288661)
EBioMedicine. 2022 Feb;76:103841. (PMID: 35085851)
J Pharm Sci. 2004 Oct;93(10):2458-75. (PMID: 15349956)
JCI Insight. 2022 Feb 8;7(3):. (PMID: 34990408)
Lancet Respir Med. 2022 Aug;10(8):739-748. (PMID: 35605625)
Front Immunol. 2022 Jun 10;13:860399. (PMID: 35757753)
N Engl J Med. 2021 Dec 16;385(25):2348-2360. (PMID: 34587382)
Antimicrob Agents Chemother. 1994 Dec;38(12):2785-91. (PMID: 7695263)
Lancet Respir Med. 2022 Aug;10(8):749-760. (PMID: 35644168)
Cell Rep. 2021 May 4;35(5):109055. (PMID: 33905739)
N Engl J Med. 2004 Feb 26;350(9):896-903. (PMID: 14985487)
BMJ Open. 2015 Oct 28;5(10):e008748. (PMID: 26510727)
EBioMedicine. 2022 Jan;75:103788. (PMID: 34954658)
Vaccines (Basel). 2021 Sep 07;9(9):. (PMID: 34579235)
Biotechnol Bioeng. 2022 Jan;119(1):48-58. (PMID: 34585736)
Sci Rep. 2015 Nov 18;5:16756. (PMID: 26576856)
Lancet. 2021 Dec 19;396(10267):1979-1993. (PMID: 33220855)
N Engl J Med. 2021 Jun 3;384(22):2092-2101. (PMID: 33835769)
Front Immunol. 2021 Oct 12;12:744887. (PMID: 34712232)
Proc Natl Acad Sci U S A. 2015 Jun 23;112(25):7809-14. (PMID: 26056267)
Lancet Infect Dis. 2020 Apr;20(4):435-444. (PMID: 31978354)
Cell Rep Med. 2021 Apr 20;2(4):100230. (PMID: 33754147)
Thorax. 2022 Feb;77(2):203-209. (PMID: 34404754)
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
الوصف
تدمد:2352-3964
DOI:10.1016/j.ebiom.2022.104298