PMID- 35043093
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220501
IS  - 2589-5370 (Electronic)
IS  - 2589-5370 (Linking)
VI  - 44
DP  - 2022 Feb
TI  - Safety and immunogenicity of a self-amplifying RNA vaccine against COVID-19: 
      COVAC1, a phase I, dose-ranging trial.
PG  - 101262
LID - 10.1016/j.eclinm.2021.101262 [doi]
LID - 101262
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 19(th) June to 28(th) October 
      2020. Participants received two intramuscular (IM) injections of LNP-nCoVsaRNA at 
      six different dose levels, 0.1-10.0mug, 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; 
      0.1mug) to 61% (14/23; 10.0mug) in ELISA and 46% (18/39; 0.3mug) to 87% (20/23; 
      5.0mug and 10.0mug) in a post-hoc immunoblot assay. Geometric mean (GM) anti-S IgG 
      concentrations ranged from 74 (95% CI, 45-119) at 0.1mug to 1023 (468-2236) ng/mL 
      at 5.0mug (p<0.001) and was not higher at 10.0mug. Neutralisation of SARS-CoV-2 by 
      participant sera was measurable in 15% (6/39; 0.1mug) to 48% (11/23; 5.0mug) 
      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 optimise humoral responses are required to 
      realise its potential as an effective vaccine against SARS-CoV-2. FUNDING: 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.
CI  - (c) 2021 The Authors.
FAU - Pollock, Katrina M
AU  - Pollock KM
AD  - Department of Infectious Disease, Imperial College London.
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.
FAU - Szubert, Alexander J
AU  - Szubert AJ
AD  - MRC Clinical Trials Unit at UCL, London, UK.
FAU - Libri, Vincenzo
AU  - Libri V
AD  - NIHR UCLH Clinical Research Facility and NIHR UCLH Biomedical Research Centre, 
      London, UK.
FAU - Boffito, Marta
AU  - Boffito M
AD  - Department of Infectious Disease, Imperial College London.
AD  - Chelsea & Westminster Hospital, London.
FAU - Owen, David
AU  - Owen D
AD  - NIHR Imperial Clinical Research Facility and NIHR Imperial Biomedical Research 
      Centre, London, UK.
FAU - Bern, Henry
AU  - Bern H
AD  - MRC Clinical Trials Unit at UCL, London, UK.
FAU - O'Hara, Jessica
AU  - O'Hara J
AD  - Department of Infectious Disease, Imperial College London.
FAU - McFarlane, Leon R
AU  - McFarlane LR
AD  - Department of Infectious Disease, Imperial College London.
FAU - Lemm, Nana-Marie
AU  - Lemm NM
AD  - Department of Infectious Disease, Imperial College London.
FAU - McKay, Paul F
AU  - McKay PF
AD  - Department of Infectious Disease, Imperial College London.
FAU - Rampling, Tommy
AU  - Rampling T
AD  - NIHR UCLH Clinical Research Facility and NIHR UCLH Biomedical Research Centre, 
      London, UK.
FAU - Yim, Yee Ting N
AU  - Yim YTN
AD  - NIHR UCLH Clinical Research Facility and NIHR UCLH Biomedical Research Centre, 
      London, UK.
FAU - Milinkovic, Ana
AU  - Milinkovic A
AD  - Chelsea & Westminster Hospital, London.
FAU - Kingsley, Cherry
AU  - Kingsley C
AD  - Department of Infectious Disease, Imperial College London.
FAU - Cole, Tom
AU  - Cole T
AD  - NIHR Imperial Clinical Research Facility and NIHR Imperial Biomedical Research 
      Centre, London, UK.
FAU - Fagerbrink, Susanne
AU  - Fagerbrink S
AD  - NIHR Imperial Clinical Research Facility and NIHR Imperial Biomedical Research 
      Centre, London, UK.
FAU - Aban, Marites
AU  - Aban M
AD  - NIHR Imperial Clinical Research Facility and NIHR Imperial Biomedical Research 
      Centre, London, UK.
FAU - Tanaka, Maniola
AU  - Tanaka M
AD  - NIHR Imperial Clinical Research Facility and NIHR Imperial Biomedical Research 
      Centre, London, UK.
FAU - Mehdipour, Savviz
AU  - Mehdipour S
AD  - NIHR Imperial Clinical Research Facility and NIHR Imperial Biomedical Research 
      Centre, London, UK.
FAU - Robbins, Alexander
AU  - Robbins A
AD  - NIHR Imperial Clinical Research Facility and NIHR Imperial Biomedical Research 
      Centre, London, UK.
FAU - Budd, William
AU  - Budd W
AD  - NIHR Imperial Clinical Research Facility and NIHR Imperial Biomedical Research 
      Centre, 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; Faculty of 
      Medicine and Institute for Life Sciences, University of Southampton, Southampton, 
      UK.
FAU - Hassanin, Hana
AU  - Hassanin H
AD  - Surrey Clinical Research Facility, Faculty of Health and Medical Sciences, 
      University of Surrey, Guildford, UK.
FAU - Cosgrove, Catherine A
AU  - Cosgrove CA
AD  - Centre for Infection, St George's, University of London, London, United Kingdom.
FAU - Winston, Alan
AU  - Winston A
AD  - Department of Infectious Disease, Imperial College London.
FAU - Fidler, Sarah
AU  - Fidler S
AD  - Department of Infectious Disease, Imperial College London.
FAU - Dunn, David T
AU  - Dunn DT
AD  - MRC Clinical Trials Unit at UCL, London, UK.
FAU - McCormack, Sheena
AU  - McCormack S
AD  - MRC Clinical Trials Unit at UCL, London, UK.
FAU - Shattock, Robin J
AU  - Shattock RJ
AD  - Department of Infectious Disease, Imperial College London.
CN  - COVAC1 study Group
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 - 20220114
PL  - England
TA  - EClinicalMedicine
JT  - EClinicalMedicine
JID - 101733727
PMC - PMC8759012
OTO - NOTNLM
OT  - AEs, adverse events
OT  - GOI, gene of Interest
OT  - LNP, lipid nanoparticle
OT  - NSP, non-structural protein
OT  - VEEV, Venezuelan equine encephalitis virus
OT  - saRNA, self-amplifying RNA
COIS- P.F.M. and R.J.S. are co-inventors on a patent application covering this 
      SARS-CoV-2 saRNA vaccine. All the other authors have nothing to report.
FIR - Adams, Kirsty
IR  - Adams K
FIR - Amini, Fahimah
IR  - Amini F
FIR - Atako, Nafisah B
IR  - Atako NB
FIR - Bakri, Amalina
IR  - Bakri A
FIR - Barclay, Wendy
IR  - Barclay W
FIR - Brodnicki, Elizabeth
IR  - Brodnicki E
FIR - Brown, Jonathan C
IR  - Brown JC
FIR - Byrne, Ruth
IR  - Byrne R
FIR - Chilvers, Rowena
IR  - Chilvers R
FIR - Coelho, Sofia
IR  - Coelho S
FIR - Day, Suzanne
IR  - Day S
FIR - Desai, Monica
IR  - Desai M
FIR - Dorman, Eleanor
IR  - Dorman E
FIR - Elliott, Tamara
IR  - Elliott T
FIR - Flight, Katie E
IR  - Flight KE
FIR - Fletcher, James
IR  - Fletcher J
FIR - Galang, John
IR  - Galang J
FIR - Gohil, Jagruti
IR  - Gohil J
FIR - Gupta, Aneta
IR  - Gupta A
FIR - Harlow, Chris
IR  - Harlow C
FIR - Hu, Kai
IR  - Hu K
FIR - Kalyan, Mahini
IR  - Kalyan M
FIR - Lagrue, Dominic
IR  - Lagrue D
FIR - Liscano, Ely
IR  - Liscano E
FIR - Njenga, Cecilia
IR  - Njenga C
FIR - Polra, Krunal
IR  - Polra K
FIR - Powlette, Derecia A
IR  - Powlette DA
FIR - Randell, Paul
IR  - Randell P
FIR - Rauchenberger, Mary
IR  - Rauchenberger M
FIR - Redknap, Ianto
IR  - Redknap I
FIR - Ricamara, Maravic
IR  - Ricamara M
FIR - Rogers, Paul
IR  - Rogers P
FIR - Sallah, Hadijatou
IR  - Sallah H
FIR - Samnuan, Karnyart
IR  - Samnuan K
FIR - Schumacher, Michael
IR  - Schumacher M
FIR - Shah, Zareena
IR  - Shah Z
FIR - Shaw, Rachel
IR  - Shaw R
FIR - Shaw, Thomas
IR  - Shaw T
FIR - Sivapatham, Stefan
IR  - Sivapatham S
FIR - Slater, Susie
IR  - Slater S
FIR - Sorley, Kim
IR  - Sorley K
FIR - Storch, Regina
IR  - Storch R
FIR - Tan, Elizabeth
IR  - Tan E
FIR - Tan, Tricia
IR  - Tan T
FIR - Thielemans, Lieze
IR  - Thielemans L
FIR - Whitely, Sarah
IR  - Whitely S
FIR - Valentine, Charlotte
IR  - Valentine C
FIR - Varghese, Jeeva
IR  - Varghese J
FIR - Vikraman, Asha
IR  - Vikraman A
FIR - Wilkins, Martin
IR  - Wilkins M
EDAT- 2022/01/20 06:00
MHDA- 2022/01/20 06:01
PMCR- 2022/01/14
CRDT- 2022/01/19 06:58
PHST- 2021/07/28 00:00 [received]
PHST- 2021/12/08 00:00 [revised]
PHST- 2021/12/16 00:00 [accepted]
PHST- 2022/01/19 06:58 [entrez]
PHST- 2022/01/20 06:00 [pubmed]
PHST- 2022/01/20 06:01 [medline]
PHST- 2022/01/14 00:00 [pmc-release]
AID - S2589-5370(21)00543-5 [pii]
AID - 101262 [pii]
AID - 10.1016/j.eclinm.2021.101262 [doi]
PST - ppublish
SO  - EClinicalMedicine. 2022 Feb;44:101262. doi: 10.1016/j.eclinm.2021.101262. Epub 
      2022 Jan 14.