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

Autor:	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.
Jazyk:	angličtina
Zdroj:	EBioMedicine [EBioMedicine] 2022 Nov; Vol. 85, pp. 104298. Date of Electronic Publication: 2022 Oct 10.
DOI:	10.1016/j.ebiom.2022.104298
Abstrakt:	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.)
Databáze:	MEDLINE
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