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Safety and Immunogenicity of a Self-Amplifying RNA Vaccine Against COVID-19: COVAC1, a Phase I, Dose-Ranging Trial

34 Pages Posted: 16 Jun 2021

See all articles by Katrina M. Pollock

Katrina M. Pollock

Imperial College London - Department of Infectious Disease

Hannah M. Cheeseman

Imperial College London - Department of Infectious Disease

Alexander J. Szubert

University College London - MRC Clinical Trials Unit

Vincenzo Libri

NIHR UCLH Clinical Research Facility

Marta Boffito

Imperial College London

David Owen

NIHR Imperial Clinical Research Facility

Henry Bern

University College London - MRC Clinical Trials Unit

Jessica O’Hara

Imperial College London - Department of Infectious Disease

Leon R. McFarlane

Imperial College London - Department of Infectious Disease

Nana-Marie Lemm

Imperial College London

Paul F. McKay

Imperial College London

Tommy Rampling

University College London Hospitals NHS Foundation Trust - Department of Clinical Virology

Yee Ting N. Yim

University College London

Ana Milinkovic

Government of the United Kingdom - Chelsea and Westminster Hospital NHS Foundation Trust

Cherry Kingsley

Imperial College London

Tom Cole

NIHR Imperial Clinical Research Facility

Susanne Fagerbrink

NIHR Imperial Clinical Research Facility

Marites Aban

NIHR Imperial Clinical Research Facility

Maniola Tanaka

NIHR Imperial Clinical Research Facility

Savviz Mehdipour

NIHR Imperial Clinical Research Facility

Alexander Robbins

NIHR Imperial Clinical Research Facility

William Budd

NIHR Imperial Clinical Research Facility

Saul N. Faust

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

Hana Hassanin

University of Surrey - Surrey Clinical Research Centre

Catherine A. Cosgrove

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

Alan Winston

Imperial College London - Department of Infectious Disease

Sarah Fidler

Imperial College London - Section of Virology

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

Summary: Lipid nanoparticle (LNP) encapsulated self-amplifying RNA (saRNA) is a novel technology formulated as a low dose vaccine against COVID-19.

Methods: A phase I first-in-human dose-ranging trial of a saRNA COVID-19 vaccine candidate LNP-nCoVsaRNA, was conducted at Imperial Clinical Research Facility, and participating centres in London, UK. Participants received two intramuscular (IM) injections of LNP-nCoVsaRNA at six different dose levels, 0·1-10·0mg, given four weeks apart. An open-label dose escalation was followed by a dose evaluation. Solicited adverse events (AEs) were collected for one week from enrolment, with follow-up at regular intervals (1-8 weeks). The binding and neutralisation capacity of anti-SARS-CoV-2 antibody raised in participant sera was measured by means of an anti-Spike (S) IgG ELISA, immunoblot, SARS-CoV-2 pseudoneutralisation and wild type neutralisation assays.

Findings: 192 healthy individuals with no history or serological evidence of COVID-19, aged 18-45 years were enrolled. The vaccine was well tolerated with no serious adverse events related to vaccination. Seroconversion at week six whether measured by ELISA or immunoblot was related to dose (both p<0·001), ranging from 8% to 61% in ELISA and 46% to 87% in the immunoblot assay.

Concurrent anti-S IgG ranged from GM concentration (95% CI) 74 (45-119) at 0·1mg to 1023 (468-2236) ng/ml at 5·0mg (p<0·001) and was not higher at 10·0mg. Neutralisation of SARS-CoV-2 by participant sera was measurable in 15-48% depending on dose level received.

Interpretation: Encapsulated saRNA is safe for clinical development and is immunogenic at low dose levels. Modifications to optimise humoral responses are required to realise its potential as an effective vaccine against SARS-CoV-2.

Trial Registration: (ISRCTN17072692, EudraCT 2020-001646-20)

Funding Statement: Medical Research Council UKRI (MC_PC_19076 and MC_UU_12023/23), National Institute for Health Research, Partners of Citadel and Citadel Securities, Sir Joseph Hotung Charitable Settlement, Jon Moulton Charity Trust.

Declaration of Interests: P.F.M. and R.J.S. are co-inventors on a patent application covering this SARS-CoV-2 saRNA vaccine. All other authors have nothing to declare.

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).

Suggested Citation

Pollock, Katrina M. and Cheeseman, Hannah M. and Szubert, Alexander J. and Libri, Vincenzo and Boffito, Marta and Owen, David and Bern, Henry and O’Hara, Jessica and McFarlane, Leon R. and Lemm, Nana-Marie and McKay, Paul F. and Rampling, Tommy and Yim, Yee Ting N. and Milinkovic, Ana and Kingsley, Cherry and Cole, Tom and Fagerbrink, Susanne and Aban, Marites and Tanaka, Maniola and Mehdipour, Savviz and Robbins, Alexander and Budd, William and Faust, Saul N. and Hassanin, Hana and Cosgrove, Catherine A. and Winston, Alan and Fidler, Sarah and Dunn, David T. and McCormack, Sheena and Shattock, Robin John, Safety and Immunogenicity of a Self-Amplifying RNA Vaccine Against COVID-19: COVAC1, a Phase I, Dose-Ranging Trial. Available at SSRN: https://ssrn.com/abstract=3859294 or http://dx.doi.org/10.2139/ssrn.3859294

Katrina M. Pollock

Imperial College London - Department of Infectious Disease ( email )

Hannah M. Cheeseman

Imperial College London - Department of Infectious Disease ( email )

Alexander J. Szubert

University College London - MRC Clinical Trials Unit ( email )

Vincenzo Libri

NIHR UCLH Clinical Research Facility

Marta Boffito

Imperial College London ( email )

South Kensington Campus
Exhibition Road
London, SW7 2AZ
United Kingdom

David Owen

NIHR Imperial Clinical Research Facility

Du Cane Rd
Shepherd's Bush
London, W12 0HS
United Kingdom

Henry Bern

University College London - MRC Clinical Trials Unit ( email )

Jessica O’Hara

Imperial College London - Department of Infectious Disease ( email )

Leon R. McFarlane

Imperial College London - Department of Infectious Disease ( email )

Nana-Marie Lemm

Imperial College London ( email )

South Kensington Campus
Exhibition Road
London, SW7 2AZ
United Kingdom

Paul F. McKay

Imperial College London ( email )

South Kensington Campus
Exhibition Road
London, SW7 2AZ
United Kingdom

Tommy Rampling

University College London Hospitals NHS Foundation Trust - Department of Clinical Virology

United Kingdom

Yee Ting N. Yim

University College London ( email )

Gower Street
London, WC1E 6BT
United Kingdom

Ana Milinkovic

Government of the United Kingdom - Chelsea and Westminster Hospital NHS Foundation Trust ( email )

London
United Kingdom

Cherry Kingsley

Imperial College London ( email )

South Kensington Campus
Exhibition Road
London, SW7 2AZ
United Kingdom

Tom Cole

NIHR Imperial Clinical Research Facility

Du Cane Rd
Shepherd's Bush
London, W12 0HS
United Kingdom

Susanne Fagerbrink

NIHR Imperial Clinical Research Facility ( email )

Du Cane Rd
Shepherd's Bush
London, W12 0HS
United Kingdom

Marites Aban

NIHR Imperial Clinical Research Facility ( email )

Du Cane Rd
Shepherd's Bush
London, W12 0HS
United Kingdom

Maniola Tanaka

NIHR Imperial Clinical Research Facility ( email )

Du Cane Rd
Shepherd's Bush
London, W12 0HS
United Kingdom

Savviz Mehdipour

NIHR Imperial Clinical Research Facility ( email )

Du Cane Rd
Shepherd's Bush
London, W12 0HS
United Kingdom

Alexander Robbins

NIHR Imperial Clinical Research Facility

Du Cane Rd
Shepherd's Bush
London, W12 0HS
United Kingdom

William Budd

NIHR Imperial Clinical Research Facility ( email )

Du Cane Rd
Shepherd's Bush
London, W12 0HS
United Kingdom

Saul N. Faust

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

Southampton
United Kingdom

Hana Hassanin

University of Surrey - Surrey Clinical Research Centre

Egerton Road
Guildford, Surrey, England GU2 7XP
United Kingdom

Catherine A. Cosgrove

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

Alan Winston

Imperial College London - Department of Infectious Disease ( email )

Sarah Fidler

Imperial College London - Section of Virology ( 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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