AUTHOR=Lucchesi Simone , Montesi Giorgio , Polvere Jacopo , Fiorino Fabio , Pastore Gabiria , Sambo Margherita , Lusini Marialetizia , Montagnani Francesca , Ciabattini Annalisa , Santoro Francesco , Garosi Guido , Medaglini Donata 

TITLE=Transcriptomic analysis after SARS-CoV-2 mRNA vaccination reveals a specific gene signature in low-responder hemodialysis patients

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1508659

DOI=10.3389/fimmu.2025.1508659

ISSN=1664-3224

ABSTRACT=IntroductionIndividuals with comorbidities, such as chronic kidney disease and hemodialysis patients (HDP), are particularly susceptible to severe COVID-19 and to its complications. Furthermore, their immune response to vaccines is impaired, requiring tailored vaccination strategies. In this study, we investigated through transcriptomic profiling the immune response heterogeneity of HDP vaccinated with two doses of mRNA BNT162b2 vaccine.MethodsTranscriptomic analyses were conducted in peripheral blood mononuclear cells (PBMC) collected from HDP and healthy controls (HC) before and 7 days after each dose. The HDP were stratified into high- and low-responders based on their humoral response after the second dose.ResultsSignificant differences in gene expression related to B cell abundance and regulation, CD4 T cell proliferation, and inflammation pathways were observed at baseline and day 7 between HDP-low responders and HC, while the HDP high-responders displayed an intermediate expression profile for these genes.DiscussionResults were consistent with the known immunologic alterations occurring in HDP cohorts related to lymphopenia, chronic inflammation, and dysregulated proliferation of CD4+. Our analyses identified an early transcriptional signature correlated with a diminished immune response in HDP low-responders, highlighting the importance of conducting a characterization of immunocompromised cohorts.