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COVAC1 Phase 2a Expanded Safety and Immunogenicity Study of a Self-Amplifying RNA Vaccine Against SARS-CoV-2

33 Pages Posted: 27 Sep 2022

See all articles by Alexander J. Szubert

Alexander J. Szubert

University College London - MRC Clinical Trials Unit

Katrina M. Pollock

Imperial College London - Department of Infectious Disease

Hannah M. Cheeseman

Imperial College London - Department of Infectious Disease

Jasmini Alagaratnam

Imperial College London - Department of Infectious Disease

Henry Bern

University College London - MRC Clinical Trials Unit

Olivia Bird

St George’s University London - St George’s Vaccine Institute

Marta Boffito

Government of the United Kingdom - Department of HIV/GUM

Ruth Byrne

Government of the United Kingdom - Department of HIV/GUM

Tom Cole

NIHR Imperial Clinical Research Facility - NIHR Imperial Biomedical Research Centre

Catherine A. Cosgrove

St George’s University London - St George’s Vaccine Institute

Saul N. Faust

University of Southampton - NIHR Southampton Clinical Research Facility and Biomedical Research Centre

Sarah Fidler

Imperial College London - Section of Virology

Eva Galiza

St George’s University London - St George’s Vaccine Institute

Hana Hassanin

University of Surrey - Surrey Clinical Research Centre

Mohini Kalyan

Imperial College London - Department of Infectious Disease

Vincenzo Libri

NIHR UCLH Clinical Research Facility

Leon R. McFarlane

Imperial College London - Department of Infectious Disease

Ana Milinkovic

Chelsea and Westminster Hospital NHS FT

Jessica O’Hara

Imperial College London - Department of Infectious Disease

David R. Owen

NIHR Imperial Clinical Research Facility - NIHR Imperial Biomedical Research Centre

Daniel Owens

University of Southampton - NIHR Southampton Clinical Research Facility and Biomedical Research Centre

Mihaela Pacurar

University Hospital Southampton - NIHR Southampton Biomedical Research Centre

Tommy Rampling

University College London - Comprehensive Biomedical Research Centre

Simon S. Skene

University of Surrey - Surrey Clinical Research Centre

Alan Winston

Imperial College London - Department of Infectious Disease

James Woolley

University of Surrey - Surrey Clinical Research Centre

Yee Ting N. Yim

University College London - Comprehensive Biomedical Research Centre

David T. Dunn

University College London - MRC Clinical Trials Unit

Sheena McCormack

University College London - MRC Clinical Trials Unit

Robin John Shattock

Imperial College London - Department of Infectious Disease

More...

Abstract

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

Szubert, Alexander J. and Pollock, Katrina M. and Cheeseman, Hannah M. and Alagaratnam, Jasmini and Bern, Henry and Bird, Olivia and Boffito, Marta and Byrne, Ruth and Cole, Tom and Cosgrove, Catherine A. and Faust, Saul N. and Fidler, Sarah and Galiza, Eva and Hassanin, Hana and Kalyan, Mohini and Libri, Vincenzo and McFarlane, Leon R. and Milinkovic, Ana and O’Hara, Jessica and Owen, David R. and Owens, Daniel and Pacurar, Mihaela and Rampling, Tommy and Skene, Simon S. and Winston, Alan and Woolley, James and Yim, Yee Ting N. and Dunn, David T. and McCormack, Sheena and Shattock, Robin John, COVAC1 Phase 2a Expanded Safety and Immunogenicity Study of a Self-Amplifying RNA Vaccine Against SARS-CoV-2. Available at SSRN: https://ssrn.com/abstract=4231236 or http://dx.doi.org/10.2139/ssrn.4231236

Alexander J. Szubert

University College London - MRC Clinical Trials Unit ( email )

Katrina M. Pollock

Imperial College London - Department of Infectious Disease ( email )

Hannah M. Cheeseman

Imperial College London - Department of Infectious Disease ( email )

Jasmini Alagaratnam

Imperial College London - Department of Infectious Disease ( email )

Henry Bern

University College London - MRC Clinical Trials Unit ( email )

Olivia Bird

St George’s University London - St George’s Vaccine Institute ( email )

Marta Boffito

Government of the United Kingdom - Department of HIV/GUM ( email )

Ruth Byrne

Government of the United Kingdom - Department of HIV/GUM ( email )

Tom Cole

NIHR Imperial Clinical Research Facility - NIHR Imperial Biomedical Research Centre ( email )

Catherine A. Cosgrove

St George’s University London - St George’s Vaccine Institute ( email )

Saul N. Faust

University of Southampton - NIHR Southampton Clinical Research Facility and Biomedical Research Centre ( email )

Southampton
United Kingdom

Sarah Fidler

Imperial College London - Section of Virology ( email )

Eva Galiza

St George’s University London - St George’s Vaccine Institute ( email )

Hana Hassanin

University of Surrey - Surrey Clinical Research Centre ( email )

Mohini Kalyan

Imperial College London - Department of Infectious Disease ( email )

Vincenzo Libri

NIHR UCLH Clinical Research Facility

Leon R. McFarlane

Imperial College London - Department of Infectious Disease ( email )

Ana Milinkovic

Chelsea and Westminster Hospital NHS FT ( email )

Jessica O’Hara

Imperial College London - Department of Infectious Disease ( email )

David R. Owen

NIHR Imperial Clinical Research Facility - NIHR Imperial Biomedical Research Centre ( email )

Daniel Owens

University of Southampton - NIHR Southampton Clinical Research Facility and Biomedical Research Centre ( email )

Mihaela Pacurar

University Hospital Southampton - NIHR Southampton Biomedical Research Centre ( email )

Tommy Rampling

University College London - Comprehensive Biomedical Research Centre ( email )

Simon S. Skene

University of Surrey - Surrey Clinical Research Centre ( email )

Alan Winston

Imperial College London - Department of Infectious Disease ( email )

James Woolley

University of Surrey - Surrey Clinical Research Centre ( email )

Yee Ting N. Yim

University College London - Comprehensive Biomedical Research Centre ( email )

David T. Dunn

University College London - MRC Clinical Trials Unit ( email )

Sheena McCormack

University College London - MRC Clinical Trials Unit ( email )

Robin John Shattock (Contact Author)

Imperial College London - Department of Infectious Disease ( email )

Exhibition Road
London, SW7 2AZ
United Kingdom

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