SARS-CoV-2 mRNA Dual Immunization Induces Innate Transcriptional Signatures, Establishes T-Cell Memory and Coordinates the Recall Response
Background: mRNA vaccines have played a crucial role in controlling the SARS-CoV-2 global pandemic. However, the immunological mechanisms involved in the induction, magnitude and longevity of mRNA-vaccine-induced protective immunity are still unclear. Methods: In our study, we used whole-RNA sequenc...
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MDPI AG
2023-01-01
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Online Access: | https://www.mdpi.com/2076-393X/11/1/103 |
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author | Ioanna Papadatou Maria Geropeppa Kleio-Maria Verrou Marianna Tzanoudaki Theano Lagousi Emmanouil Liatsis Vana Spoulou |
author_facet | Ioanna Papadatou Maria Geropeppa Kleio-Maria Verrou Marianna Tzanoudaki Theano Lagousi Emmanouil Liatsis Vana Spoulou |
author_sort | Ioanna Papadatou |
collection | DOAJ |
description | Background: mRNA vaccines have played a crucial role in controlling the SARS-CoV-2 global pandemic. However, the immunological mechanisms involved in the induction, magnitude and longevity of mRNA-vaccine-induced protective immunity are still unclear. Methods: In our study, we used whole-RNA sequencing along with detailed immunophenotyping of antigen-specific T cells and humoral RBD-specific response to dual immunization with the Pfizer–BioNTech mRNA vaccine (BNT162b2) and correlated them with response to an additional dose, administered 10 months later, in order to comprehensively profile the immune response of healthy volunteers to BNT162b2. Results: Primary dual immunization induced upregulation of the Type I interferon pathway and generated spike protein (S)-specific IFN-γ+ and TNF-α+ CD4 T cells, S-specific memory CD4 T cells, and RBD-specific antibodies against SARS-CoV-2. S-specific CD4 T cells induced by the primary series correlated with the RBD-specific antibody titers to a third dose. Conclusions: This study demonstrates the induction of both innate and adaptive immunity in response to the BNT162b2 mRNA vaccine in a coordinated manner and identifies the central role of primarily induced CD4+ T cells as a predictive biomarker of the magnitude of anamnestic immune response. |
first_indexed | 2024-03-09T11:03:49Z |
format | Article |
id | doaj.art-0b4facfbf6964e2d8d18c95bdab6f319 |
institution | Directory Open Access Journal |
issn | 2076-393X |
language | English |
last_indexed | 2024-03-09T11:03:49Z |
publishDate | 2023-01-01 |
publisher | MDPI AG |
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series | Vaccines |
spelling | doaj.art-0b4facfbf6964e2d8d18c95bdab6f3192023-12-01T01:02:25ZengMDPI AGVaccines2076-393X2023-01-0111110310.3390/vaccines11010103SARS-CoV-2 mRNA Dual Immunization Induces Innate Transcriptional Signatures, Establishes T-Cell Memory and Coordinates the Recall ResponseIoanna Papadatou0Maria Geropeppa1Kleio-Maria Verrou2Marianna Tzanoudaki3Theano Lagousi4Emmanouil Liatsis5Vana Spoulou6First Department of Paediatrics, Medical School, “Aghia Sophia” Children’s Hospital, National and Kapodistrian University of Athens, 11527 Athens, GreeceImmunobiology and Vaccinology Research Lab, Medical School, National and Kapodistrian University of Athens, 11527 Athens, GreeceCenter of New Biotechnologies & Precision Medicine, Medical School, National and Kapodistrian University of Athens, 11527 Athens, GreeceDepartment of Immunology and Histocompatibility, Specialized Center and Referral Center for Primary Immunodeficiencies, Paediatric Immunology, “Aghia Sophia” Children’s Hospital, 11527 Athens, GreeceFirst Department of Paediatrics, Medical School, “Aghia Sophia” Children’s Hospital, National and Kapodistrian University of Athens, 11527 Athens, GreeceDepartment of Immunology and Histocompatibility, Specialized Center and Referral Center for Primary Immunodeficiencies, Paediatric Immunology, “Aghia Sophia” Children’s Hospital, 11527 Athens, GreeceFirst Department of Paediatrics, Medical School, “Aghia Sophia” Children’s Hospital, National and Kapodistrian University of Athens, 11527 Athens, GreeceBackground: mRNA vaccines have played a crucial role in controlling the SARS-CoV-2 global pandemic. However, the immunological mechanisms involved in the induction, magnitude and longevity of mRNA-vaccine-induced protective immunity are still unclear. Methods: In our study, we used whole-RNA sequencing along with detailed immunophenotyping of antigen-specific T cells and humoral RBD-specific response to dual immunization with the Pfizer–BioNTech mRNA vaccine (BNT162b2) and correlated them with response to an additional dose, administered 10 months later, in order to comprehensively profile the immune response of healthy volunteers to BNT162b2. Results: Primary dual immunization induced upregulation of the Type I interferon pathway and generated spike protein (S)-specific IFN-γ+ and TNF-α+ CD4 T cells, S-specific memory CD4 T cells, and RBD-specific antibodies against SARS-CoV-2. S-specific CD4 T cells induced by the primary series correlated with the RBD-specific antibody titers to a third dose. Conclusions: This study demonstrates the induction of both innate and adaptive immunity in response to the BNT162b2 mRNA vaccine in a coordinated manner and identifies the central role of primarily induced CD4+ T cells as a predictive biomarker of the magnitude of anamnestic immune response.https://www.mdpi.com/2076-393X/11/1/103SARS-CoV-2 vaccineimmunological memorytranscriptomicssystems vaccinology |
spellingShingle | Ioanna Papadatou Maria Geropeppa Kleio-Maria Verrou Marianna Tzanoudaki Theano Lagousi Emmanouil Liatsis Vana Spoulou SARS-CoV-2 mRNA Dual Immunization Induces Innate Transcriptional Signatures, Establishes T-Cell Memory and Coordinates the Recall Response Vaccines SARS-CoV-2 vaccine immunological memory transcriptomics systems vaccinology |
title | SARS-CoV-2 mRNA Dual Immunization Induces Innate Transcriptional Signatures, Establishes T-Cell Memory and Coordinates the Recall Response |
title_full | SARS-CoV-2 mRNA Dual Immunization Induces Innate Transcriptional Signatures, Establishes T-Cell Memory and Coordinates the Recall Response |
title_fullStr | SARS-CoV-2 mRNA Dual Immunization Induces Innate Transcriptional Signatures, Establishes T-Cell Memory and Coordinates the Recall Response |
title_full_unstemmed | SARS-CoV-2 mRNA Dual Immunization Induces Innate Transcriptional Signatures, Establishes T-Cell Memory and Coordinates the Recall Response |
title_short | SARS-CoV-2 mRNA Dual Immunization Induces Innate Transcriptional Signatures, Establishes T-Cell Memory and Coordinates the Recall Response |
title_sort | sars cov 2 mrna dual immunization induces innate transcriptional signatures establishes t cell memory and coordinates the recall response |
topic | SARS-CoV-2 vaccine immunological memory transcriptomics systems vaccinology |
url | https://www.mdpi.com/2076-393X/11/1/103 |
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