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

著者: Meera Madhavan, Adam 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 Ewer, Alexander D. Douglas - EBioMedicine 2022 被引用: 146

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: 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.