Szubert, AJ;
Pollock, KM;
Cheeseman, HM;
Alagaratnam, J;
Bern, H;
Bird, O;
Boffito, M;
Byrne, R;
Cole, T;
Cosgrove, CA;
et al.
Szubert, AJ; Pollock, KM; Cheeseman, HM; Alagaratnam, J; Bern, H; Bird, O; Boffito, M; Byrne, R; Cole, T; Cosgrove, CA; Faust, SN; Fidler, S; Galiza, E; Hassanin, H; Kalyan, M; Libri, V; McFarlane, LR; Milinkovic, A; O'Hara, J; Owen, DR; Owens, D; Pacurar, M; Rampling, T; Skene, S; Winston, A; Woolley, J; Yim, YTN; Dunn, DT; McCormack, S; Shattock, RJ; COVAC 1 Study Team
(2023)
COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2.
EClinicalMedicine, 56.
p. 101823.
ISSN 2589-5370
https://doi.org/10.1016/j.eclinm.2022.101823
SGUL Authors: Cosgrove, Catherine
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.
Item Type: |
Article
|
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, COVAC 1 Study Team, Clinical trial, Immunogenicity, Safety, SARS-CoV-2, Self-amplifying RNA, Vaccine |
SGUL Research Institute / Research Centre: |
Academic Structure > Infection and Immunity Research Institute (INII) |
Journal or Publication Title: |
EClinicalMedicine |
ISSN: |
2589-5370 |
Language: |
eng |
Dates: |
Date | Event |
---|
February 2023 | Published | 13 January 2023 | Published Online | 23 December 2022 | Accepted |
|
Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
|
PubMed ID: |
36684396 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/115173 |
Publisher's version: |
https://doi.org/10.1016/j.eclinm.2022.101823 |
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