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Immunogenicity mechanism of mRNA vaccines and their limitations in promoting adaptive protection against SARS-CoV-2

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) in late 2019, hundreds of millions of people have been infected worldwide. There have been unprecedented efforts in acquiring effective vaccines to confer p...

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Autores principales: Salleh, Mohd Zulkifli, Norazmi, Mohd Nor, Deris, Zakuan Zainy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8917804/
https://www.ncbi.nlm.nih.gov/pubmed/35287350
http://dx.doi.org/10.7717/peerj.13083
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author Salleh, Mohd Zulkifli
Norazmi, Mohd Nor
Deris, Zakuan Zainy
author_facet Salleh, Mohd Zulkifli
Norazmi, Mohd Nor
Deris, Zakuan Zainy
author_sort Salleh, Mohd Zulkifli
collection PubMed
description Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) in late 2019, hundreds of millions of people have been infected worldwide. There have been unprecedented efforts in acquiring effective vaccines to confer protection against the disease. mRNA vaccines have emerged as promising alternatives to conventional vaccines due to their high potency with the capacity for rapid development and low manufacturing costs. In this review, we summarize the currently available vaccines against SARS-CoV-2 in development, with the focus on the concepts of mRNA vaccines, their antigen selection, delivery and optimization to increase the immunostimulatory capability of mRNA as well as its stability and translatability. We also discuss the host immune responses to the SARS-CoV-2 infection and expound in detail, the adaptive immune response upon immunization with mRNA vaccines, in which high levels of spike-specific IgG and neutralizing antibodies were detected after two-dose vaccination. mRNA vaccines have been shown to induce a robust CD8(+)T cell response, with a balanced CD4(+) T(H)1/T(H)2 response. We further discuss the challenges and limitations of COVID-19 mRNA vaccines, where newly emerging variants of SARS-CoV-2 may render currently deployed vaccines less effective. Imbalanced and inappropriate inflammatory responses, resulting from hyper-activation of pro-inflammatory cytokines, which may lead to vaccine-associated enhanced respiratory disease (VAERD) and rare cases of myocarditis and pericarditis also are discussed.
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spelling pubmed-89178042022-03-13 Immunogenicity mechanism of mRNA vaccines and their limitations in promoting adaptive protection against SARS-CoV-2 Salleh, Mohd Zulkifli Norazmi, Mohd Nor Deris, Zakuan Zainy PeerJ Molecular Biology Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) in late 2019, hundreds of millions of people have been infected worldwide. There have been unprecedented efforts in acquiring effective vaccines to confer protection against the disease. mRNA vaccines have emerged as promising alternatives to conventional vaccines due to their high potency with the capacity for rapid development and low manufacturing costs. In this review, we summarize the currently available vaccines against SARS-CoV-2 in development, with the focus on the concepts of mRNA vaccines, their antigen selection, delivery and optimization to increase the immunostimulatory capability of mRNA as well as its stability and translatability. We also discuss the host immune responses to the SARS-CoV-2 infection and expound in detail, the adaptive immune response upon immunization with mRNA vaccines, in which high levels of spike-specific IgG and neutralizing antibodies were detected after two-dose vaccination. mRNA vaccines have been shown to induce a robust CD8(+)T cell response, with a balanced CD4(+) T(H)1/T(H)2 response. We further discuss the challenges and limitations of COVID-19 mRNA vaccines, where newly emerging variants of SARS-CoV-2 may render currently deployed vaccines less effective. Imbalanced and inappropriate inflammatory responses, resulting from hyper-activation of pro-inflammatory cytokines, which may lead to vaccine-associated enhanced respiratory disease (VAERD) and rare cases of myocarditis and pericarditis also are discussed. PeerJ Inc. 2022-03-09 /pmc/articles/PMC8917804/ /pubmed/35287350 http://dx.doi.org/10.7717/peerj.13083 Text en ©2022 Salleh 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, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Molecular Biology
Salleh, Mohd Zulkifli
Norazmi, Mohd Nor
Deris, Zakuan Zainy
Immunogenicity mechanism of mRNA vaccines and their limitations in promoting adaptive protection against SARS-CoV-2
title Immunogenicity mechanism of mRNA vaccines and their limitations in promoting adaptive protection against SARS-CoV-2
title_full Immunogenicity mechanism of mRNA vaccines and their limitations in promoting adaptive protection against SARS-CoV-2
title_fullStr Immunogenicity mechanism of mRNA vaccines and their limitations in promoting adaptive protection against SARS-CoV-2
title_full_unstemmed Immunogenicity mechanism of mRNA vaccines and their limitations in promoting adaptive protection against SARS-CoV-2
title_short Immunogenicity mechanism of mRNA vaccines and their limitations in promoting adaptive protection against SARS-CoV-2
title_sort immunogenicity mechanism of mrna vaccines and their limitations in promoting adaptive protection against sars-cov-2
topic Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8917804/
https://www.ncbi.nlm.nih.gov/pubmed/35287350
http://dx.doi.org/10.7717/peerj.13083
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