Cargando…

Immune gene expression analysis indicates the potential of a self-amplifying Covid-19 mRNA vaccine

Remarkable potency has been demonstrated for mRNA vaccines in reducing the global burden of the ongoing COVID-19 pandemic. An alternative form of the mRNA vaccine is the self-amplifying mRNA (sa-mRNA) vaccine, which encodes an alphavirus replicase that self-amplifies the full-length mRNA and SARS-Co...

Descripción completa

Detalles Bibliográficos
Autores principales: Ong, Eugenia Z., Yee, Jia Xin, Ooi, Justin S. G., Syenina, Ayesa, de Alwis, Ruklanthi, Chen, Shiwei, Sim, Jean X. Y., Kalimuddin, Shirin, Leong, Yan Shan, Chan, Yvonne F. Z., Sekulovich, Rose, Sullivan, Brian M., Lindert, Kelly, Sullivan, Sean B., Chivukula, Pad, Hughes, Steven G., Low, Jenny G., Ooi, Eng Eong, Chan, Kuan Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9703414/
https://www.ncbi.nlm.nih.gov/pubmed/36443317
http://dx.doi.org/10.1038/s41541-022-00573-y
_version_ 1784839842012594176
author Ong, Eugenia Z.
Yee, Jia Xin
Ooi, Justin S. G.
Syenina, Ayesa
de Alwis, Ruklanthi
Chen, Shiwei
Sim, Jean X. Y.
Kalimuddin, Shirin
Leong, Yan Shan
Chan, Yvonne F. Z.
Sekulovich, Rose
Sullivan, Brian M.
Lindert, Kelly
Sullivan, Sean B.
Chivukula, Pad
Hughes, Steven G.
Low, Jenny G.
Ooi, Eng Eong
Chan, Kuan Rong
author_facet Ong, Eugenia Z.
Yee, Jia Xin
Ooi, Justin S. G.
Syenina, Ayesa
de Alwis, Ruklanthi
Chen, Shiwei
Sim, Jean X. Y.
Kalimuddin, Shirin
Leong, Yan Shan
Chan, Yvonne F. Z.
Sekulovich, Rose
Sullivan, Brian M.
Lindert, Kelly
Sullivan, Sean B.
Chivukula, Pad
Hughes, Steven G.
Low, Jenny G.
Ooi, Eng Eong
Chan, Kuan Rong
author_sort Ong, Eugenia Z.
collection PubMed
description Remarkable potency has been demonstrated for mRNA vaccines in reducing the global burden of the ongoing COVID-19 pandemic. An alternative form of the mRNA vaccine is the self-amplifying mRNA (sa-mRNA) vaccine, which encodes an alphavirus replicase that self-amplifies the full-length mRNA and SARS-CoV-2 spike (S) transgene. However, early-phase clinical trials of sa-mRNA COVID-19 vaccine candidates have questioned the potential of this platform to develop potent vaccines. We examined the immune gene response to a candidate sa-mRNA vaccine against COVID-19, ARCT-021, and compared our findings to the host response to other forms of vaccines. In blood samples from healthy volunteers that participated in a phase I/II clinical trial, greater induction of transcripts involved in Toll-like receptor (TLR) signalling, antigen presentation and complement activation at 1 day post-vaccination was associated with higher anti-S antibody titers. Conversely, transcripts involved in T-cell maturation at day 7 post-vaccination informed the magnitude of eventual S-specific T-cell responses. The transcriptomic signature for ARCT-021 vaccination strongly correlated with live viral vector vaccines, adjuvanted vaccines and BNT162b2 1 day post-vaccination. Moreover, the ARCT-021 signature correlated with day 7 YF17D live-attenuated vaccine transcriptomic responses. Altogether, our findings show that sa-mRNA vaccination induces innate immune responses that are associated with the development of adaptive immunity from other forms of vaccines, supporting further development of this vaccine platform for clinical application.
format Online
Article
Text
id pubmed-9703414
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-97034142022-11-28 Immune gene expression analysis indicates the potential of a self-amplifying Covid-19 mRNA vaccine Ong, Eugenia Z. Yee, Jia Xin Ooi, Justin S. G. Syenina, Ayesa de Alwis, Ruklanthi Chen, Shiwei Sim, Jean X. Y. Kalimuddin, Shirin Leong, Yan Shan Chan, Yvonne F. Z. Sekulovich, Rose Sullivan, Brian M. Lindert, Kelly Sullivan, Sean B. Chivukula, Pad Hughes, Steven G. Low, Jenny G. Ooi, Eng Eong Chan, Kuan Rong NPJ Vaccines Article Remarkable potency has been demonstrated for mRNA vaccines in reducing the global burden of the ongoing COVID-19 pandemic. An alternative form of the mRNA vaccine is the self-amplifying mRNA (sa-mRNA) vaccine, which encodes an alphavirus replicase that self-amplifies the full-length mRNA and SARS-CoV-2 spike (S) transgene. However, early-phase clinical trials of sa-mRNA COVID-19 vaccine candidates have questioned the potential of this platform to develop potent vaccines. We examined the immune gene response to a candidate sa-mRNA vaccine against COVID-19, ARCT-021, and compared our findings to the host response to other forms of vaccines. In blood samples from healthy volunteers that participated in a phase I/II clinical trial, greater induction of transcripts involved in Toll-like receptor (TLR) signalling, antigen presentation and complement activation at 1 day post-vaccination was associated with higher anti-S antibody titers. Conversely, transcripts involved in T-cell maturation at day 7 post-vaccination informed the magnitude of eventual S-specific T-cell responses. The transcriptomic signature for ARCT-021 vaccination strongly correlated with live viral vector vaccines, adjuvanted vaccines and BNT162b2 1 day post-vaccination. Moreover, the ARCT-021 signature correlated with day 7 YF17D live-attenuated vaccine transcriptomic responses. Altogether, our findings show that sa-mRNA vaccination induces innate immune responses that are associated with the development of adaptive immunity from other forms of vaccines, supporting further development of this vaccine platform for clinical application. Nature Publishing Group UK 2022-11-28 /pmc/articles/PMC9703414/ /pubmed/36443317 http://dx.doi.org/10.1038/s41541-022-00573-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ong, Eugenia Z.
Yee, Jia Xin
Ooi, Justin S. G.
Syenina, Ayesa
de Alwis, Ruklanthi
Chen, Shiwei
Sim, Jean X. Y.
Kalimuddin, Shirin
Leong, Yan Shan
Chan, Yvonne F. Z.
Sekulovich, Rose
Sullivan, Brian M.
Lindert, Kelly
Sullivan, Sean B.
Chivukula, Pad
Hughes, Steven G.
Low, Jenny G.
Ooi, Eng Eong
Chan, Kuan Rong
Immune gene expression analysis indicates the potential of a self-amplifying Covid-19 mRNA vaccine
title Immune gene expression analysis indicates the potential of a self-amplifying Covid-19 mRNA vaccine
title_full Immune gene expression analysis indicates the potential of a self-amplifying Covid-19 mRNA vaccine
title_fullStr Immune gene expression analysis indicates the potential of a self-amplifying Covid-19 mRNA vaccine
title_full_unstemmed Immune gene expression analysis indicates the potential of a self-amplifying Covid-19 mRNA vaccine
title_short Immune gene expression analysis indicates the potential of a self-amplifying Covid-19 mRNA vaccine
title_sort immune gene expression analysis indicates the potential of a self-amplifying covid-19 mrna vaccine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9703414/
https://www.ncbi.nlm.nih.gov/pubmed/36443317
http://dx.doi.org/10.1038/s41541-022-00573-y
work_keys_str_mv AT ongeugeniaz immunegeneexpressionanalysisindicatesthepotentialofaselfamplifyingcovid19mrnavaccine
AT yeejiaxin immunegeneexpressionanalysisindicatesthepotentialofaselfamplifyingcovid19mrnavaccine
AT ooijustinsg immunegeneexpressionanalysisindicatesthepotentialofaselfamplifyingcovid19mrnavaccine
AT syeninaayesa immunegeneexpressionanalysisindicatesthepotentialofaselfamplifyingcovid19mrnavaccine
AT dealwisruklanthi immunegeneexpressionanalysisindicatesthepotentialofaselfamplifyingcovid19mrnavaccine
AT chenshiwei immunegeneexpressionanalysisindicatesthepotentialofaselfamplifyingcovid19mrnavaccine
AT simjeanxy immunegeneexpressionanalysisindicatesthepotentialofaselfamplifyingcovid19mrnavaccine
AT kalimuddinshirin immunegeneexpressionanalysisindicatesthepotentialofaselfamplifyingcovid19mrnavaccine
AT leongyanshan immunegeneexpressionanalysisindicatesthepotentialofaselfamplifyingcovid19mrnavaccine
AT chanyvonnefz immunegeneexpressionanalysisindicatesthepotentialofaselfamplifyingcovid19mrnavaccine
AT sekulovichrose immunegeneexpressionanalysisindicatesthepotentialofaselfamplifyingcovid19mrnavaccine
AT sullivanbrianm immunegeneexpressionanalysisindicatesthepotentialofaselfamplifyingcovid19mrnavaccine
AT lindertkelly immunegeneexpressionanalysisindicatesthepotentialofaselfamplifyingcovid19mrnavaccine
AT sullivanseanb immunegeneexpressionanalysisindicatesthepotentialofaselfamplifyingcovid19mrnavaccine
AT chivukulapad immunegeneexpressionanalysisindicatesthepotentialofaselfamplifyingcovid19mrnavaccine
AT hughessteveng immunegeneexpressionanalysisindicatesthepotentialofaselfamplifyingcovid19mrnavaccine
AT lowjennyg immunegeneexpressionanalysisindicatesthepotentialofaselfamplifyingcovid19mrnavaccine
AT ooiengeong immunegeneexpressionanalysisindicatesthepotentialofaselfamplifyingcovid19mrnavaccine
AT chankuanrong immunegeneexpressionanalysisindicatesthepotentialofaselfamplifyingcovid19mrnavaccine