Imperial College London
Alternate

Dr David R Owen MD PhD

Faculty of Medicine, Department of Brain Sciences

Reader in Molecular Pharmacology and Experimental Medicine
 
 
 
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Contact

 

+44 (0)20 3313 6195d.owen Website

 
 
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Location

 

G20AICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Pollock:2022:10.1016/j.eclinm.2021.101262,
author = {Pollock, KM and Cheeseman, HM and Szubert, AJ and Libri, V and Boffito, M and Owen, D and Bern, H and O'Hara, J and McFarlane, LR and Lemm, N-M and McKay, PF and Rampling, T and Yim, YTN and Milinkovic, A and Kingsley, C and Cole, T and Fagerbrink, S and Aban, M and Tanaka, M and Mehdipour, S and Robbins, A and Budd, W and Faust, SN and Hassanin, H and Cosgrove, CA and Winston, A and Fidler, S and Dunn, DT and McCormack, S and Shattock, RJ and COVAC1, study Group},
doi = {10.1016/j.eclinm.2021.101262},
journal = {EClinicalMedicine},
title = {Safety and immunogenicity of a self-amplifying RNA vaccine against COVID-19: COVAC1, a phase I, dose-ranging trial},
url = {http://dx.doi.org/10.1016/j.eclinm.2021.101262},
volume = {44},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background: 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, between 19th June to 28th October 2020. Participants received two intramuscular (IM) injections of LNP-nCoVsaRNA at six different dose levels, 0.1-10.0μg, 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. (The trial is registered: ISRCTN17072692, EudraCT 2020-001646-20). 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% (3/39; 0.1μg) to 61% (14/23; 10.0μg) in ELISA and 46% (18/39; 0.3μg) to 87% (20/23; 5.0μg and 10.0μg) in a post-hoc immunoblot assay. Geometric mean (GM) anti-S IgG concentrations ranged from 74 (95% CI, 45-119) at 0.1μg to 1023 (468-2236) ng/mL at 5.0μg (p<0.001) and was not higher at 10.0μg. Neutralisation of SARS-CoV-2 by participant sera was measurable in 15% (6/39; 0.1μg) to 48% (11/23; 5.0μg) depending on dose level received. Interpretation: Encapsulated saRNA is safe for clinical development, is immunogenic at low dose levels but failed to induce 100% seroconversion. Modifications to optimis
AU  - Pollock,KM
AU  - Cheeseman,HM
AU  - Szubert,AJ
AU  - Libri,V
AU  - Boffito,M
AU  - Owen,D
AU  - Bern,H
AU  - O'Hara,J
AU  - McFarlane,LR
AU  - Lemm,N-M
AU  - McKay,PF
AU  - Rampling,T
AU  - Yim,YTN
AU  - Milinkovic,A
AU  - Kingsley,C
AU  - Cole,T
AU  - Fagerbrink,S
AU  - Aban,M
AU  - Tanaka,M
AU  - Mehdipour,S
AU  - Robbins,A
AU  - Budd,W
AU  - Faust,SN
AU  - Hassanin,H
AU  - Cosgrove,CA
AU  - Winston,A
AU  - Fidler,S
AU  - Dunn,DT
AU  - McCormack,S
AU  - Shattock,RJ
AU  - COVAC1,study Group
DO  - 10.1016/j.eclinm.2021.101262
PY  - 2022///
SN  - 2589-5370
TI  - Safety and immunogenicity of a self-amplifying RNA vaccine against COVID-19: COVAC1, a phase I, dose-ranging trial
T2  - EClinicalMedicine
UR  - http://dx.doi.org/10.1016/j.eclinm.2021.101262
UR  - https://www.ncbi.nlm.nih.gov/pubmed/35043093
UR  - http://hdl.handle.net/10044/1/94153
VL  - 44
ER  -
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