Tolerability and immunogenicity of an intranasally-administered adenovirus-vectored COVID-19 vaccine: An open-label partially-randomised ascending dose phase I trial
Meera Madhavan,
Adam J. Ritchie,
Jeremy Aboagye,
Daniel Jenkin,
Samuel Provstgaad-Morys,
Iona Tarbet,
Danielle Woods,
Sophie Davies,
Megan Baker,
Abigail Platt,
Amy Flaxman,
Holly Smith,
Sandra Belij-Rammerstorfer,
Deidre Wilkins,
Elizabeth J. Kelly,
Tonya Villafana,
Justin A. Green,
Ian Poulton,
Teresa Lambe,
Adrian V.S. Hill,
Katie J. Ewer,
Alexander D. Douglas
Affiliations
Meera Madhavan
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
Adam J. Ritchie
Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK
Jeremy Aboagye
Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK
Daniel Jenkin
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
Samuel Provstgaad-Morys
Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK
Iona Tarbet
Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK
Danielle Woods
Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK
Sophie Davies
Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK
Megan Baker
Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK
Abigail Platt
Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK
Amy Flaxman
Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK
Holly Smith
Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK
Sandra Belij-Rammerstorfer
Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK
Deidre Wilkins
Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, 1 Medimmune Way, Gaithersburg, MD 20878, USA
Elizabeth J. Kelly
Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, 1 Medimmune Way, Gaithersburg, MD 20878, USA
Tonya Villafana
Clinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA
Justin A. Green
Clinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK
Ian Poulton
Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK
Teresa Lambe
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
Adrian V.S. Hill
Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK
Katie J. Ewer
Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK
Alexander D. Douglas
Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7BN, UK; Corresponding author.
Summary: 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 × 109 viral particles (VP, n=6), 2 × 1010 VP (n=12), or 5 × 1010 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 × 1010 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.
