| Title: |
COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2 |
| Authors: |
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 |
| Contributors: |
Team, COVAC 1 Study |
| Publisher Information: |
Elsevier |
| Publication Year: |
2025 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
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 ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.1016/j.eclinm.2022.101823 |
| DOI: |
10.1016/j.eclinm.2022.101823 |
| Availability: |
https://doi.org/10.1016/j.eclinm.2022.101823; https://ora.ox.ac.uk/objects/uuid:af7c30bf-352c-43b2-a550-337e75c7675a |
| Rights: |
info:eu-repo/semantics/openAccess ; CC Attribution (CC BY) |
| Accession Number: |
edsbas.6C65200 |
| Database: |
BASE |