Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Papadatou, Ioanna, Geropeppa, Maria, Verrou, Kleio-Maria, Tzanoudaki, Marianna, Lagousi, Theano, Liatsis, Emmanouil, Spoulou, Vana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9861479/
https://www.ncbi.nlm.nih.gov/pubmed/36679948
http://dx.doi.org/10.3390/vaccines11010103
_version_ 1784874851921559552
author Papadatou, Ioanna
Geropeppa, Maria
Verrou, Kleio-Maria
Tzanoudaki, Marianna
Lagousi, Theano
Liatsis, Emmanouil
Spoulou, Vana
author_facet Papadatou, Ioanna
Geropeppa, Maria
Verrou, Kleio-Maria
Tzanoudaki, Marianna
Lagousi, Theano
Liatsis, Emmanouil
Spoulou, Vana
author_sort Papadatou, Ioanna
collection PubMed
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.
format Online
Article
Text
id pubmed-9861479
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-98614792023-01-22 SARS-CoV-2 mRNA Dual Immunization Induces Innate Transcriptional Signatures, Establishes T-Cell Memory and Coordinates the Recall Response Papadatou, Ioanna Geropeppa, Maria Verrou, Kleio-Maria Tzanoudaki, Marianna Lagousi, Theano Liatsis, Emmanouil Spoulou, Vana Vaccines (Basel) Article 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. MDPI 2023-01-01 /pmc/articles/PMC9861479/ /pubmed/36679948 http://dx.doi.org/10.3390/vaccines11010103 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Papadatou, Ioanna
Geropeppa, Maria
Verrou, Kleio-Maria
Tzanoudaki, Marianna
Lagousi, Theano
Liatsis, Emmanouil
Spoulou, Vana
SARS-CoV-2 mRNA Dual Immunization Induces Innate Transcriptional Signatures, Establishes T-Cell Memory and Coordinates the Recall Response
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9861479/
https://www.ncbi.nlm.nih.gov/pubmed/36679948
http://dx.doi.org/10.3390/vaccines11010103
work_keys_str_mv AT papadatouioanna sarscov2mrnadualimmunizationinducesinnatetranscriptionalsignaturesestablishestcellmemoryandcoordinatestherecallresponse
AT geropeppamaria sarscov2mrnadualimmunizationinducesinnatetranscriptionalsignaturesestablishestcellmemoryandcoordinatestherecallresponse
AT verroukleiomaria sarscov2mrnadualimmunizationinducesinnatetranscriptionalsignaturesestablishestcellmemoryandcoordinatestherecallresponse
AT tzanoudakimarianna sarscov2mrnadualimmunizationinducesinnatetranscriptionalsignaturesestablishestcellmemoryandcoordinatestherecallresponse
AT lagousitheano sarscov2mrnadualimmunizationinducesinnatetranscriptionalsignaturesestablishestcellmemoryandcoordinatestherecallresponse
AT liatsisemmanouil sarscov2mrnadualimmunizationinducesinnatetranscriptionalsignaturesestablishestcellmemoryandcoordinatestherecallresponse
AT spoulouvana sarscov2mrnadualimmunizationinducesinnatetranscriptionalsignaturesestablishestcellmemoryandcoordinatestherecallresponse