PMID- 36684396 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240228 IS - 2589-5370 (Electronic) IS - 2589-5370 (Linking) VI - 56 DP - 2023 Feb TI - COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2. PG - 101823 LID - 10.1016/j.eclinm.2022.101823 [doi] LID - 101823 AB - 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 mug then 10 mug of LNP-nCoVsaRNA, approximately 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 mug followed by 10.0 mug 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 naive 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 mug 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 naive 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 mug followed by 10.0 mug. Boosting of S IgG antibodies was observed with a single 1.0 mug 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. CI - (c) 2022 The Author(s). FAU - Szubert, Alex J AU - Szubert AJ AD - cMRC Clinical Trials Unit at UCL, London, UK. FAU - Pollock, Katrina M AU - Pollock KM AD - Department of Infectious Disease, Imperial College London, UK. AD - NIHR Imperial Clinical Research Facility and NIHR Imperial Biomedical Research Centre, London, UK. FAU - Cheeseman, Hannah M AU - Cheeseman HM AD - Department of Infectious Disease, Imperial College London, UK. FAU - Alagaratnam, Jasmini AU - Alagaratnam J AD - Department of Infectious Disease, Imperial College London, UK. FAU - Bern, Henry AU - Bern H AD - cMRC Clinical Trials Unit at UCL, London, UK. FAU - Bird, Olivia AU - Bird O AD - St George's Vaccine Institute, Institute for Infection and Immunity, St George's University of London, UK. FAU - Boffito, Marta AU - Boffito M AD - Chelsea & Westminster Hospital, London, UK. FAU - Byrne, Ruth AU - Byrne R AD - Chelsea & Westminster Hospital, London, UK. FAU - Cole, Tom AU - Cole T AD - NIHR Imperial Clinical Research Facility and NIHR Imperial Biomedical Research Centre, London, UK. FAU - Cosgrove, Catherine A AU - Cosgrove CA AD - St George's Vaccine Institute, Institute for Infection and Immunity, St George's University of London, UK. FAU - Faust, Saul N AU - Faust SN AD - NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK. AD - Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK. FAU - Fidler, Sarah AU - Fidler S AD - Department of Infectious Disease, Imperial College London, UK. FAU - Galiza, Eva AU - Galiza E AD - St George's Vaccine Institute, Institute for Infection and Immunity, St George's University of London, UK. FAU - Hassanin, Hana AU - Hassanin H AD - Surrey Clinical Research Facility, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK. FAU - Kalyan, Mohini AU - Kalyan M AD - Department of Infectious Disease, Imperial College London, UK. FAU - Libri, Vincenzo AU - Libri V AD - dNIHR UCLH Clinical Research Facility and NIHR UCLH Biomedical Research Centre, London, UK. FAU - McFarlane, Leon R AU - McFarlane LR AD - Department of Infectious Disease, Imperial College London, UK. FAU - Milinkovic, Ana AU - Milinkovic A AD - Chelsea & Westminster Hospital, London, UK. FAU - O'Hara, Jessica AU - O'Hara J AD - Department of Infectious Disease, Imperial College London, UK. FAU - Owen, David R AU - Owen DR AD - NIHR Imperial Clinical Research Facility and NIHR Imperial Biomedical Research Centre, London, UK. AD - Department of Brain Sciences, Imperial College London, London, UK. FAU - Owens, Daniel AU - Owens D AD - NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK. AD - Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK. FAU - Pacurar, Mihaela AU - Pacurar M AD - NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK. AD - Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK. FAU - Rampling, Tommy AU - Rampling T AD - dNIHR UCLH Clinical Research Facility and NIHR UCLH Biomedical Research Centre, London, UK. FAU - Skene, Simon AU - Skene S AD - Surrey Clinical Research Facility, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK. FAU - Winston, Alan AU - Winston A AD - Department of Infectious Disease, Imperial College London, UK. FAU - Woolley, James AU - Woolley J AD - Surrey Clinical Research Facility, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK. FAU - Yim, Yee Ting N AU - Yim YTN AD - dNIHR UCLH Clinical Research Facility and NIHR UCLH Biomedical Research Centre, London, UK. FAU - Dunn, David T AU - Dunn DT AD - cMRC Clinical Trials Unit at UCL, London, UK. FAU - McCormack, Sheena AU - McCormack S AD - cMRC Clinical Trials Unit at UCL, London, UK. FAU - Shattock, Robin J AU - Shattock RJ AD - Department of Infectious Disease, Imperial College London, UK. CN - COVAC 1 Study Team LA - eng GR - MC_PC_19076/MRC_/Medical Research Council/United Kingdom GR - MC_UU_00004/04/MRC_/Medical Research Council/United Kingdom GR - MR/N008219/1/MRC_/Medical Research Council/United Kingdom GR - MR/T031891/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article DEP - 20230113 PL - England TA - EClinicalMedicine JT - EClinicalMedicine JID - 101733727 PMC - PMC9837478 OTO - NOTNLM OT - Clinical trial OT - Immunogenicity OT - SARS-CoV-2 OT - Safety OT - Self-amplifying RNA OT - Vaccine COIS- 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. EDAT- 2023/01/24 06:00 MHDA- 2023/01/24 06:01 PMCR- 2023/01/13 CRDT- 2023/01/23 04:23 PHST- 2022/09/26 00:00 [received] PHST- 2022/12/22 00:00 [revised] PHST- 2022/12/23 00:00 [accepted] PHST- 2023/01/23 04:23 [entrez] PHST- 2023/01/24 06:00 [pubmed] PHST- 2023/01/24 06:01 [medline] PHST- 2023/01/13 00:00 [pmc-release] AID - S2589-5370(22)00552-1 [pii] AID - 101823 [pii] AID - 10.1016/j.eclinm.2022.101823 [doi] PST - epublish SO - EClinicalMedicine. 2023 Jan 13;56:101823. doi: 10.1016/j.eclinm.2022.101823. eCollection 2023 Feb.