COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2. (February 2023)

• Record Type: Journal Article
• Authors: Szubert, Alex J.; Pollock, Katrina M.; Cheeseman, Hannah M.; Alagaratnam, Jasmini; Bern, Henry; Bird, Olivia; Boffito, Marta; Byrne, Ruth; Cole, Tom; Cosgrove, Catherine A.; Faust, Saul N.; Fidler, Sarah; Galiza, Eva; Hassanin, Hana; Kalyan, Mohini; Libri, Vincenzo; McFarlane, Leon R.; Milinkovic, Ana; O'Hara, Jessica; Owen, David R.; Owens, Daniel; Pacurar, Mihaela; Rampling, Tommy; Skene, Simon; Winston, Alan; Woolley, James; Yim, Yee Ting N.; Dunn, David T.; McCormack, Sheena; Shattock, Robin J.
• Is Part Of: EClinicalMedicine. Volume 56(2023)
• Publication Date: 2023-02
• Subjects: Self-amplifying RNA -- Vaccine -- SARS-CoV-2 -- Clinical trial -- Safety -- Immunogenicity; Medicine -- Research -- Periodicals; Medical policy -- Periodicals; Clinical Medicine; Health Policy; Public Health; Medical policy; Medicine -- Research; Periodical; Electronic journals; Periodicals; 613
• DOI: 10.1016/j.eclinm.2022.101823
• Languages: English
• ISSNs: 2589-5370

Abstract

Summary: 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 .