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Enhanced immune responses following heterologous vaccination with self-amplifying RNA and mRNA COVID-19 vaccines

The optimal vaccination strategy to boost responses in the context of pre-existing immune memory to the SARS-CoV-2 spike (S) glycoprotein is an important question for global public health. To address this, we explored the SARS-CoV-2-specific humoral and cellular immune responses to a novel self-ampl...

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Autores principales: Elliott, Tamara, Cheeseman, Hannah M., Evans, Abbey B., Day, Suzanne, McFarlane, Leon R., O’Hara, Jessica, Kalyan, Mohini, Amini, Fahimah, Cole, Tom, Winston, Alan, Fidler, Sarah, Pollock, Katrina M., Harker, James A., Shattock, Robin J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9565686/
https://www.ncbi.nlm.nih.gov/pubmed/36194628
http://dx.doi.org/10.1371/journal.ppat.1010885
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author Elliott, Tamara
Cheeseman, Hannah M.
Evans, Abbey B.
Day, Suzanne
McFarlane, Leon R.
O’Hara, Jessica
Kalyan, Mohini
Amini, Fahimah
Cole, Tom
Winston, Alan
Fidler, Sarah
Pollock, Katrina M.
Harker, James A.
Shattock, Robin J.
author_facet Elliott, Tamara
Cheeseman, Hannah M.
Evans, Abbey B.
Day, Suzanne
McFarlane, Leon R.
O’Hara, Jessica
Kalyan, Mohini
Amini, Fahimah
Cole, Tom
Winston, Alan
Fidler, Sarah
Pollock, Katrina M.
Harker, James A.
Shattock, Robin J.
author_sort Elliott, Tamara
collection PubMed
description The optimal vaccination strategy to boost responses in the context of pre-existing immune memory to the SARS-CoV-2 spike (S) glycoprotein is an important question for global public health. To address this, we explored the SARS-CoV-2-specific humoral and cellular immune responses to a novel self-amplifying RNA (saRNA) vaccine followed by a UK authorised mRNA vaccine (BNT162b2) in individuals with and without previous COVID-19, and compared these responses with those who received an authorised vaccine alone. 35 subjects receiving saRNA (saRNA group) as part of the COVAC1 clinical trial and an additional 40 participants receiving an authorised SARS-CoV-2 vaccine only (non-saRNA group) were recruited. Antibody responses were measured by ELISA and a pseudoneutralisation assay for wildtype, Delta and Omicron variants. Cellular responses were measured by IFN-ƴ ELISpot and an activation induced marker (AIM) assay. Approximately 50% in each group had previous COVID-19 prior to vaccination, confirmed by PCR or antibody positivity on ELISA. All of those who received saRNA subsequently received a full course of an authorised vaccine. The majority (83%) of those receiving saRNA who were COVID-19 naïve at baseline seroconverted following the second dose, and those with previous COVID-19 had an increase in antibody titres two weeks following saRNA vaccination (median 27-fold), however titres were lower when compared to mRNA vaccination. Two weeks following the 2(nd) authorised mRNA vaccine dose, binding and neutralising antibody titres were significantly higher in the saRNA participants with previous COVID-19, compared to non-saRNA, or COVID-19 naive saRNA participants. Cellular responses were again highest in this group, with a higher proportion of spike specific CD8+ than CD4+ T cells when compared to those receiving the mRNA vaccine only. These findings suggest an immunological benefit of increased antigen exposure, both from natural infection and vaccination, particularly evident in those receiving heterologous vaccination with saRNA and mRNA.
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spelling pubmed-95656862022-10-15 Enhanced immune responses following heterologous vaccination with self-amplifying RNA and mRNA COVID-19 vaccines Elliott, Tamara Cheeseman, Hannah M. Evans, Abbey B. Day, Suzanne McFarlane, Leon R. O’Hara, Jessica Kalyan, Mohini Amini, Fahimah Cole, Tom Winston, Alan Fidler, Sarah Pollock, Katrina M. Harker, James A. Shattock, Robin J. PLoS Pathog Research Article The optimal vaccination strategy to boost responses in the context of pre-existing immune memory to the SARS-CoV-2 spike (S) glycoprotein is an important question for global public health. To address this, we explored the SARS-CoV-2-specific humoral and cellular immune responses to a novel self-amplifying RNA (saRNA) vaccine followed by a UK authorised mRNA vaccine (BNT162b2) in individuals with and without previous COVID-19, and compared these responses with those who received an authorised vaccine alone. 35 subjects receiving saRNA (saRNA group) as part of the COVAC1 clinical trial and an additional 40 participants receiving an authorised SARS-CoV-2 vaccine only (non-saRNA group) were recruited. Antibody responses were measured by ELISA and a pseudoneutralisation assay for wildtype, Delta and Omicron variants. Cellular responses were measured by IFN-ƴ ELISpot and an activation induced marker (AIM) assay. Approximately 50% in each group had previous COVID-19 prior to vaccination, confirmed by PCR or antibody positivity on ELISA. All of those who received saRNA subsequently received a full course of an authorised vaccine. The majority (83%) of those receiving saRNA who were COVID-19 naïve at baseline seroconverted following the second dose, and those with previous COVID-19 had an increase in antibody titres two weeks following saRNA vaccination (median 27-fold), however titres were lower when compared to mRNA vaccination. Two weeks following the 2(nd) authorised mRNA vaccine dose, binding and neutralising antibody titres were significantly higher in the saRNA participants with previous COVID-19, compared to non-saRNA, or COVID-19 naive saRNA participants. Cellular responses were again highest in this group, with a higher proportion of spike specific CD8+ than CD4+ T cells when compared to those receiving the mRNA vaccine only. These findings suggest an immunological benefit of increased antigen exposure, both from natural infection and vaccination, particularly evident in those receiving heterologous vaccination with saRNA and mRNA. Public Library of Science 2022-10-04 /pmc/articles/PMC9565686/ /pubmed/36194628 http://dx.doi.org/10.1371/journal.ppat.1010885 Text en © 2022 Elliott et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Elliott, Tamara
Cheeseman, Hannah M.
Evans, Abbey B.
Day, Suzanne
McFarlane, Leon R.
O’Hara, Jessica
Kalyan, Mohini
Amini, Fahimah
Cole, Tom
Winston, Alan
Fidler, Sarah
Pollock, Katrina M.
Harker, James A.
Shattock, Robin J.
Enhanced immune responses following heterologous vaccination with self-amplifying RNA and mRNA COVID-19 vaccines
title Enhanced immune responses following heterologous vaccination with self-amplifying RNA and mRNA COVID-19 vaccines
title_full Enhanced immune responses following heterologous vaccination with self-amplifying RNA and mRNA COVID-19 vaccines
title_fullStr Enhanced immune responses following heterologous vaccination with self-amplifying RNA and mRNA COVID-19 vaccines
title_full_unstemmed Enhanced immune responses following heterologous vaccination with self-amplifying RNA and mRNA COVID-19 vaccines
title_short Enhanced immune responses following heterologous vaccination with self-amplifying RNA and mRNA COVID-19 vaccines
title_sort enhanced immune responses following heterologous vaccination with self-amplifying rna and mrna covid-19 vaccines
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9565686/
https://www.ncbi.nlm.nih.gov/pubmed/36194628
http://dx.doi.org/10.1371/journal.ppat.1010885
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