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COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2

Szubert, Alex J; Pollock, Katrina M; Cheeseman, Hannah M; Alagaratnam, Jasmini; Bern, Henry; Bird, Olivia; Boffito, Marta; ... COVAC 1 Study Team; + view all (2023) COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2. EClinicalMedicine , 56 , Article 101823. 10.1016/j.eclinm.2022.101823. Green open access

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Abstract

BACKGROUND: Lipid nanoparticle (LNP) encapsulated self-amplifying RNA (saRNA) is well tolerated and immunogenic in SARS-CoV-2 seronegative and seropositive individuals aged 18-75. METHODS: A phase 2a expanded safety and immunogenicity study of a saRNA SARS-CoV-2 vaccine candidate LNP-nCoVsaRNA, was conducted at participating centres in the UK between 10th August 2020 and 30th July 2021. Participants received 1 μg then 10 μg of LNP-nCoVsaRNA, ∼14 weeks apart. Solicited adverse events (AEs) were collected for one week post-each vaccine, and unsolicited AEs throughout. Binding and neutralisating anti-SARS-CoV-2 antibody raised in participant sera was measured by means of an anti-Spike (S) IgG ELISA, and SARS-CoV-2 pseudoneutralisation assay. (The trial is registered: ISRCTN17072692, EudraCT 2020-001646-20). FINDINGS: 216 healthy individuals (median age 51 years) received 1.0 μg followed by 10.0 μg of the vaccine. 28/216 participants were either known to have previous SARS-CoV2 infection and/or were positive for anti-Spike (S) IgG at baseline. Reactogenicity was as expected based on the reactions following licensed COVID-19 vaccines, and there were no serious AEs related to vaccination. 80% of baseline SARS-CoV-2 naïve individuals (147/183) seroconverted two weeks post second immunization, irrespective of age (18-75); 56% (102/183) had detectable neutralising antibodies. Almost all (28/31) SARS-CoV-2 positive individuals had increased S IgG binding antibodies following their first 1.0 μg dose with a ≥0.5log10 increase in 71% (22/31). INTERPRETATION: Encapsulated saRNA was well tolerated and immunogenic in adults aged 18-75 years. Seroconversion rates in antigen naïve were higher than those reported in our dose-ranging study. Further work is required to determine if this difference is related to a longer dosing interval (14 vs. 4 weeks) or dosing with 1.0 μg followed by 10.0 μg. Boosting of S IgG antibodies was observed with a single 1.0 μg injection in those with pre-existing immune responses. FUNDING: Grants and gifts from the Medical Research Council UKRI (MC_PC_19076), the National Institute for Health Research/Vaccine Task Force, Partners of Citadel and Citadel Securities, Sir Joseph Hotung Charitable Settlement, Jon Moulton Charity Trust, Pierre Andurand, and Restore the Earth.

Type: Article
Title: COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.eclinm.2022.101823
Publisher version: https://doi.org/10.1016/j.eclinm.2022.101823
Language: English
Additional information: Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Clinical trial, Immunogenicity, SARS-CoV-2, Safety, Self-amplifying RNA, Vaccine
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10163763
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