COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2

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.

Author list

Affiliations:

  1. MRC Clinical Trials Unit at UCL, London, UK
  2. Department of Infectious Disease, Imperial College London, UK
  3. St George’s Vaccine Institute, Institute for Infection and Immunity, St George’s University of London, UK
  4. Chelsea & Westminster Hospital, London, UK
  5. NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  6. Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK
  7. Surrey Clinical Research Facility, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
  8. NIHR UCLH Clinical Research Facility and NIHR UCLH Biomedical Research Centre, London, UK
  9. NIHR Imperial Clinical Research Facility and NIHR Imperial Biomedical Research Centre, London, UK
  10. Department of Brain Sciences, Imperial College London, London, UK

Authors:

Alex J. Szubert,1,11 Katrina M. Pollock,2,9,11 Hannah M. Cheeseman,2 Jasmini Alagaratnam,2 Henry Bern,1 Olivia Bird,3 Marta Boffito,4 Ruth Byrne,4 Tom Cole,9 Catherine A. Cosgrove,3 Saul N. Faust,5,6 Sarah Fidler,2 Eva Galiza,3 Hana Hassanin,7 Mohini Kalyan,2 Vincenzo Libri,8 Leon R. McFarlane,2 Ana Milinkovic,4 Jessica O’Hara,2 David R. Owen,9,10 Daniel Owens,5,6 Mihaela Pacurar,5,6 Tommy Rampling,8 Simon Skene,7 Alan Winston,2 James Woolley,7 Yee Ting N. Yim,8 David T. Dunn,1 Sheena McCormack,1,** and Robin J. Shattock,2,* on behalf of the COVAC 1 Study Team

Novel Coronavirus SARS-CoV-2

10.1016/j.eclinm.2022.101823

E Clinical Medicine

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