Safety and immunogenicity of a self-amplifying RNA vaccine against COVID-19: COVAC1, a phase I, dose-ranging trial.
AEs, adverse events
GOI, gene of Interest
LNP, lipid nanoparticle
NSP, non-structural protein
VEEV, Venezuelan equine encephalitis virus
saRNA, self-amplifying RNA
Journal
EClinicalMedicine
ISSN: 2589-5370
Titre abrégé: EClinicalMedicine
Pays: England
ID NLM: 101733727
Informations de publication
Date de publication:
Feb 2022
Feb 2022
Historique:
received:
28
07
2021
revised:
08
12
2021
accepted:
16
12
2021
entrez:
19
1
2022
pubmed:
20
1
2022
medline:
20
1
2022
Statut:
ppublish
Résumé
Lipid nanoparticle (LNP) encapsulated self-amplifying RNA (saRNA) is a novel technology formulated as a low dose vaccine against COVID-19. 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 19 192 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. 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. 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.
Sections du résumé
BACKGROUND
BACKGROUND
Lipid nanoparticle (LNP) encapsulated self-amplifying RNA (saRNA) is a novel technology formulated as a low dose vaccine against COVID-19.
METHODS
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
FINDINGS
RESULTS
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
CONCLUSIONS
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
BACKGROUND
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.
Identifiants
pubmed: 35043093
doi: 10.1016/j.eclinm.2021.101262
pii: S2589-5370(21)00543-5
pmc: PMC8759012
doi:
Types de publication
Journal Article
Langues
eng
Pagination
101262Subventions
Organisme : Medical Research Council
ID : MC_PC_19076
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00004/04
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N008219/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T031891/1
Pays : United Kingdom
Investigateurs
Kirsty Adams
(K)
Fahimah Amini
(F)
Nafisah B Atako
(NB)
Amalina Bakri
(A)
Wendy Barclay
(W)
Elizabeth Brodnicki
(E)
Jonathan C Brown
(JC)
Ruth Byrne
(R)
Rowena Chilvers
(R)
Sofia Coelho
(S)
Suzanne Day
(S)
Monica Desai
(M)
Eleanor Dorman
(E)
Tamara Elliott
(T)
Katie E Flight
(KE)
James Fletcher
(J)
John Galang
(J)
Jagruti Gohil
(J)
Aneta Gupta
(A)
Chris Harlow
(C)
Kai Hu
(K)
Mahini Kalyan
(M)
Dominic Lagrue
(D)
Ely Liscano
(E)
Cecilia Njenga
(C)
Krunal Polra
(K)
Derecia A Powlette
(DA)
Paul Randell
(P)
Mary Rauchenberger
(M)
Ianto Redknap
(I)
Maravic Ricamara
(M)
Paul Rogers
(P)
Hadijatou Sallah
(H)
Karnyart Samnuan
(K)
Michael Schumacher
(M)
Zareena Shah
(Z)
Rachel Shaw
(R)
Thomas Shaw
(T)
Stefan Sivapatham
(S)
Susie Slater
(S)
Kim Sorley
(K)
Regina Storch
(R)
Elizabeth Tan
(E)
Tricia Tan
(T)
Lieze Thielemans
(L)
Sarah Whitely
(S)
Charlotte Valentine
(C)
Jeeva Varghese
(J)
Asha Vikraman
(A)
Martin Wilkins
(M)
Informations de copyright
© 2021 The Authors.
Déclaration de conflit d'intérêts
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.
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