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COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2

BACKGROUND: 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...

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Autores principales: Szubert, Alex J., Pollock, Katrina M., Cheeseman, Hannah M., Alagaratnam, Jasmini, Bern, Henry, Bird, Olivia, Boffito, Marta, Byrne, Ruth, Cole, Tom, Cosgrove, Catherine A., Faust, Saul N., Fidler, Sarah, Galiza, Eva, Hassanin, Hana, Kalyan, Mohini, Libri, Vincenzo, McFarlane, Leon R., Milinkovic, Ana, O'Hara, Jessica, Owen, David R., Owens, Daniel, Pacurar, Mihaela, Rampling, Tommy, Skene, Simon, Winston, Alan, Woolley, James, Yim, Yee Ting N., Dunn, David T., McCormack, Sheena, Shattock, Robin J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9837478/
https://www.ncbi.nlm.nih.gov/pubmed/36684396
http://dx.doi.org/10.1016/j.eclinm.2022.101823
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author Szubert, Alex J.
Pollock, Katrina M.
Cheeseman, Hannah M.
Alagaratnam, Jasmini
Bern, Henry
Bird, Olivia
Boffito, Marta
Byrne, Ruth
Cole, Tom
Cosgrove, Catherine A.
Faust, Saul N.
Fidler, Sarah
Galiza, Eva
Hassanin, Hana
Kalyan, Mohini
Libri, Vincenzo
McFarlane, Leon R.
Milinkovic, Ana
O'Hara, Jessica
Owen, David R.
Owens, Daniel
Pacurar, Mihaela
Rampling, Tommy
Skene, Simon
Winston, Alan
Woolley, James
Yim, Yee Ting N.
Dunn, David T.
McCormack, Sheena
Shattock, Robin J.
author_facet Szubert, Alex J.
Pollock, Katrina M.
Cheeseman, Hannah M.
Alagaratnam, Jasmini
Bern, Henry
Bird, Olivia
Boffito, Marta
Byrne, Ruth
Cole, Tom
Cosgrove, Catherine A.
Faust, Saul N.
Fidler, Sarah
Galiza, Eva
Hassanin, Hana
Kalyan, Mohini
Libri, Vincenzo
McFarlane, Leon R.
Milinkovic, Ana
O'Hara, Jessica
Owen, David R.
Owens, Daniel
Pacurar, Mihaela
Rampling, Tommy
Skene, Simon
Winston, Alan
Woolley, James
Yim, Yee Ting N.
Dunn, David T.
McCormack, Sheena
Shattock, Robin J.
author_sort Szubert, Alex J.
collection PubMed
description BACKGROUND: 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 between 10th August 2020 and 30th July 2021. Participants received 1 μg then 10 μg 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. (The trial is registered: ISRCTN17072692, EudraCT 2020-001646-20). FINDINGS: 216 healthy individuals (median age 51 years) received 1.0 μg followed by 10.0 μg 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 based on the reactions following licensed COVID-19 vaccines, 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 1.0 μg 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 1.0 μg followed by 10.0 μg. Boosting of S IgG antibodies was observed with a single 1.0 μg injection in those with pre-existing immune responses. FUNDING: Grants and gifts from the 10.13039/501100000265Medical Research Council UKRI (MC_PC_19076), the 10.13039/100000002National Institute for Health Research/Vaccine Task Force, Partners of Citadel and Citadel Securities, Sir Joseph Hotung Charitable Settlement, 10.13039/501100023262Jon Moulton Charity Trust, Pierre Andurand, and Restore the Earth.
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spelling pubmed-98374782023-01-17 COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2 Szubert, Alex J. Pollock, Katrina M. Cheeseman, Hannah M. Alagaratnam, Jasmini Bern, Henry Bird, Olivia Boffito, Marta Byrne, Ruth Cole, Tom Cosgrove, Catherine A. Faust, Saul N. Fidler, Sarah Galiza, Eva Hassanin, Hana Kalyan, Mohini Libri, Vincenzo McFarlane, Leon R. Milinkovic, Ana O'Hara, Jessica Owen, David R. Owens, Daniel Pacurar, Mihaela Rampling, Tommy Skene, Simon Winston, Alan Woolley, James Yim, Yee Ting N. Dunn, David T. McCormack, Sheena Shattock, Robin J. eClinicalMedicine Articles BACKGROUND: 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 between 10th August 2020 and 30th July 2021. Participants received 1 μg then 10 μg 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. (The trial is registered: ISRCTN17072692, EudraCT 2020-001646-20). FINDINGS: 216 healthy individuals (median age 51 years) received 1.0 μg followed by 10.0 μg 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 based on the reactions following licensed COVID-19 vaccines, 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 1.0 μg 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 1.0 μg followed by 10.0 μg. Boosting of S IgG antibodies was observed with a single 1.0 μg injection in those with pre-existing immune responses. FUNDING: Grants and gifts from the 10.13039/501100000265Medical Research Council UKRI (MC_PC_19076), the 10.13039/100000002National Institute for Health Research/Vaccine Task Force, Partners of Citadel and Citadel Securities, Sir Joseph Hotung Charitable Settlement, 10.13039/501100023262Jon Moulton Charity Trust, Pierre Andurand, and Restore the Earth. Elsevier 2023-01-13 /pmc/articles/PMC9837478/ /pubmed/36684396 http://dx.doi.org/10.1016/j.eclinm.2022.101823 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Articles
Szubert, Alex J.
Pollock, Katrina M.
Cheeseman, Hannah M.
Alagaratnam, Jasmini
Bern, Henry
Bird, Olivia
Boffito, Marta
Byrne, Ruth
Cole, Tom
Cosgrove, Catherine A.
Faust, Saul N.
Fidler, Sarah
Galiza, Eva
Hassanin, Hana
Kalyan, Mohini
Libri, Vincenzo
McFarlane, Leon R.
Milinkovic, Ana
O'Hara, Jessica
Owen, David R.
Owens, Daniel
Pacurar, Mihaela
Rampling, Tommy
Skene, Simon
Winston, Alan
Woolley, James
Yim, Yee Ting N.
Dunn, David T.
McCormack, Sheena
Shattock, Robin J.
COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2
title COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2
title_full COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2
title_fullStr COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2
title_full_unstemmed COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2
title_short COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2
title_sort covac1 phase 2a expanded safety and immunogenicity study of a self-amplifying rna vaccine against sars-cov-2
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9837478/
https://www.ncbi.nlm.nih.gov/pubmed/36684396
http://dx.doi.org/10.1016/j.eclinm.2022.101823
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