B Cells Isolated from Individuals Who Do Not Respond to the HBV Vaccine Are Characterized by Higher DNA Methylation-Estimated Aging Compared to Responders
Katarzyna Malgorzata Kwiatkowska,
Simona Anticoli,
Stefano Salvioli,
Luciano Calzari,
Davide Gentilini,
Christian Albano,
Reparata Rosa Di Prinzio,
Salvatore Zaffina,
Rita Carsetti,
Anna Ruggieri,
Paolo Garagnani
Affiliations
Katarzyna Malgorzata Kwiatkowska
Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy
Simona Anticoli
Istituto Superiore di Sanità, Center for Gender Specific Medicine, 00161 Rome, Italy
Stefano Salvioli
Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy
Luciano Calzari
Bioinformatics and Statistical Genomics Unit, Istituto Auxologico Italiano IRCCS, 20095 Cusano Milanino, Italy
Davide Gentilini
Bioinformatics and Statistical Genomics Unit, Istituto Auxologico Italiano IRCCS, 20095 Cusano Milanino, Italy
Christian Albano
Immunology Research Area, B Cell Unit, Ospedale Pediatrico Bambino Gesù IRCCS, 00146 Rome, Italy
Reparata Rosa Di Prinzio
Occupational Medicine/Health Technology Assessment and Safety Research Unit, Clinical-Technological Innovations Research Area, Ospedale Pediatrico Bambino Gesù IRCCS, 00146 Rome, Italy
Salvatore Zaffina
Occupational Medicine/Health Technology Assessment and Safety Research Unit, Clinical-Technological Innovations Research Area, Ospedale Pediatrico Bambino Gesù IRCCS, 00146 Rome, Italy
Rita Carsetti
Immunology Research Area, B Cell Unit, Ospedale Pediatrico Bambino Gesù IRCCS, 00146 Rome, Italy
Anna Ruggieri
Istituto Superiore di Sanità, Center for Gender Specific Medicine, 00161 Rome, Italy
Paolo Garagnani
Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy
Healthcare workers (HCWs) are a high-risk group for hepatitis B virus (HBV) infection. Notably, about 5–10% of the general population does not respond to the HBV vaccination. In this study, we aimed to investigate DNA methylation (DNAm) in order to estimate the biological age of B cells from HCW of both sexes, either responder (R) or non-responder (NR), to HBV vaccination. We used genome-wide DNA methylation data to calculate a set of biomarkers in B cells collected from 41 Rs and 30 NRs between 22 and 62 years old. Unresponsiveness to HBV vaccination was associated with accelerated epigenetic aging (DNAmAge, AltumAge, DunedinPoAm) and was accompanied by epigenetic drift. Female non-responders had higher estimates of telomere length and lower CRP inflammation risk score when compared to responders. Overall, epigenetic differences between responders and non-responders were more evident in females than males. In this study we demonstrated that several methylation DNAm-based clocks and biomarkers are associated with an increased risk of non-response to HBV vaccination, particularly in females. Based on these results, we propose that accelerated epigenetic age could contribute to vaccine unresponsiveness. These insights may help improve the evaluation of the effectiveness of vaccination strategies, especially among HCWs and vulnerable patients.
