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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Main Authors: Ioanna Papadatou, Maria Geropeppa, Kleio-Maria Verrou, Marianna Tzanoudaki, Theano Lagousi, Emmanouil Liatsis, Vana Spoulou
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Vaccines
Subjects:
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.
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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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