Impact of mycophenolate mofetil on recombinant zoster vaccine immunogenicity in systemic sclerosis: a prospective observational study

Abstract Background: To evaluate mycophenolate mofetil (MMF) impact on humoral, cell-mediated, and cytokine/chemokine responses to the recombinant zoster vaccine (RZV) in systemic sclerosis (SSc) patients. Methods: In this prospective observational study, 16 SSc patients (8 receiving stable MMF therapy and 8 not receiving immunosuppressive treatment) and 12 healthy controls (HC) received the two-dose RZV schedule. Humoral immunity was assessed by anti-glycoprotein E (anti-gE) IgG titres, cell-mediated immunity (CMI) was evaluated by intracellular cytokine staining of gE-stimulated peripheral blood mononuclear cells. Cytokine/chemokine pathways were investigated using multiplex immunoassays and composite scores. Results: Post-vaccination anti-gE titres were significantly lower in SSc patients than in HC [median 2328 (IQR 1520–2980) vs ≥4000mIU/mL; p < 0.0001]. Within the SSc cohort, MMF-treated patients had lower antibody titres than untreated patients [1756 (891–2547) vs 2830 (2297–3408) mIU/mL; p = 0.03]. In multivariable analysis, MMF treatment (β=-1465.4, 95% CI -2298 to -632; p = 0.003) and older age (β=-33.4, 95% CI -61.9 to -4.8; p = 0.03) independently predicted lower antibody titres. In contrast, CMI was induced similarly across groups. Humoral response-related cytokines and type I interferon score correlated positively with post-vaccination antibody titres, while inflammatory cytokine score was significantly impaired by MMF. No herpes zoster reactivation or SSc worsening occurred during the 2-year follow-up. Conclusion: Our data show that MMF impairs vaccine humoral response, but not cellular immune response. Since herpes zoster reactivation mainly depends on specific T cell-mediated immunity decline over time, our study suggests that MMF can be continued during RZV schedule.