SARS-CoV-2 mRNA Dual Immunization Induces Innate Transcriptional Signatures, Establishes T-Cell Memory and Coordinates the Recall Response
Ioanna Papadatou,
Maria Geropeppa,
Kleio-Maria Verrou,
Marianna Tzanoudaki,
Theano Lagousi,
Emmanouil Liatsis,
Vana Spoulou
Affiliations
Ioanna Papadatou
First Department of Paediatrics, Medical School, “Aghia Sophia” Children’s Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
Maria Geropeppa
Immunobiology and Vaccinology Research Lab, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
Kleio-Maria Verrou
Center of New Biotechnologies & Precision Medicine, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
Marianna Tzanoudaki
Department of Immunology and Histocompatibility, Specialized Center and Referral Center for Primary Immunodeficiencies, Paediatric Immunology, “Aghia Sophia” Children’s Hospital, 11527 Athens, Greece
Theano Lagousi
First Department of Paediatrics, Medical School, “Aghia Sophia” Children’s Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
Emmanouil Liatsis
Department of Immunology and Histocompatibility, Specialized Center and Referral Center for Primary Immunodeficiencies, Paediatric Immunology, “Aghia Sophia” Children’s Hospital, 11527 Athens, Greece
Vana Spoulou
First Department of Paediatrics, Medical School, “Aghia Sophia” Children’s Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
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.
