Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact email@example.com.
COVAC1 Phase 2a Expanded Safety and Immunogenicity Study of a Self-Amplifying RNA Vaccine Against SARS-CoV-2
33 Pages Posted: 27 Sep 2022More...
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. Participants received 1mg then 10mg 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.
Findings: 216 healthy individuals (median age 51 years) received 1.0µg followed by 10.0µg 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 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 1.0µg 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 1.0µg followed by 10.0µg. Boosting of S IgG antibodies was observed with a single 1.0µg injection in those with pre-existing immune responses.
Trial Registration: This study was approved with three numbers in total: ISRCTN17072692, EudraCT 2020-001646-20 NCT04934111.
Funding Information: This study was co-funded by grants and gifts from the Medical Research Council UKRI (MC_PC_19076), and the National Institute Health Research/Vaccine Task Force, Partners of Citadel and Citadel Securities, Sir Joseph Hotung Charitable Settlement, Jon Moulton Charity Trust, Pierre Andurand, Restore the Earth.
Declaration of Interests: R.J.S. is a co-inventor on a patent application covering this SARS-CoV-2 saRNA vaccine. All the other authors have nothing to report.
Ethics Approval Statement: This study was approved in the UK by the Medicines and Healthcare products Regulatory Agency and the North East - York Research Ethics Committee (reference 20/SC/0145) (ISRCTN17072692, EudraCT 2020-001646-20). Written informed consent was obtained from all participants, and the trial conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice.
Keywords: SARS-CoV-2, vaccination, self-amplifying RNA, saRNA, immune response
Suggested Citation: Suggested Citation