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

• Published in: EBioMedicine Vol. 85; p. 104298
• Main Authors: Madhavan, Meera, Ritchie, Adam J., Aboagye, Jeremy, Jenkin, Daniel, Provstgaad-Morys, Samuel, Tarbet, Iona, Woods, Danielle, Davies, Sophie, Baker, Megan, Platt, Abigail, Flaxman, Amy, Smith, Holly, Belij-Rammerstorfer, Sandra, Wilkins, Deidre, Kelly, Elizabeth J., Villafana, Tonya, Green, Justin A., Poulton, Ian, Lambe, Teresa, Hill, Adrian V.S., Ewer, Katie J., Douglas, Alexander D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-11-2022; The Authors. Published by Elsevier B.V; Elsevier
• Subjects: Adenoviridae - genetics; Adenovirus vector; Adult; Antibodies, Viral; BNT162 Vaccine; ChAdOx1 nCoV-19; COVID-19 - prevention & control; COVID-19 Vaccines - adverse effects; Humans; Intranasal vaccination; mRNA Vaccines; Mucosal antibody; SARS-CoV-2; Vaccination - adverse effects; Viral Vaccines; Mucosal antibody; SARS-CoV-2; Intranasal vaccination; Adenovirus vector
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2022.104298

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).
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).
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.
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.
AstraZeneca.