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 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.

Is Rituximab-Associated Hypogammaglobulinemia Always Linked to B-Cell Depletion?

We describe a case of a 3-year-old male toddler with a history of severe and refractory warm antibody autoimmune hemolytic anemia (w-AIHA) since early infancy and hypogammaglobulinemia persisting 20 months after rituximab administration (second-line rescue therapy). Specifically, although peripheral blood flow cytometry B-cell population counts signified B-cell recovery following completion of rituximab therapy, IgG levels were barely detectable. Detailed laboratory evaluation did not reveal any humoral or cell-mediated immunity impairment and the patient remained asymptomatic, without any infections or recurrence of w-AIHA. Due to severe hypogammaglobulinemia, he was placed on immunoglobulin replacement therapy (IVIG). The implemented PID (primary immunodeficiency) gene panel identified only variants of uncertain significance (VUS). The aim of this report is to underline the documentation of persisting hypogammaglobulinemia after rituximab despite peripheral blood B-cell reconstitution.