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

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 chal-lenge 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-nai euro ve participants were allocated to receive 5 x 109 viral particles (VP, n=6), 2 x 1010 VP (n=12), or 5 x 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 intramus-cular doses of ChAdOx1 nCoV-19 and six who had received two intramuscular doses of BNT162b2 (Pfizer / BioN-Tech) were given a single intranasal dose of 5 x 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 vaccina-tion 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.Copyright (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)