Immunogenicity to Herpes Zoster recombinant subunit vaccine in immune-mediated rheumatic patients under treatment with JAK inhibitors

Abstract Objectives Patients with immune-mediated rheumatic diseases (IMRDs) face an elevated risk of varicella-zoster virus infection (VZV) and herpes zoster (HZ). Treatment with immunosuppressors further increases the risk. A new recently approved adjuvant recombinant inactive vaccine offers safe protection against HZ. However, limited data exist on the efficacy of this new vaccine in patients with IMRDs treated with JAK inhibitors (JAK-i). We aimed to characterize B- and T-cell immune responses elicited by the HZ recombinant subunit vaccine in patients with IMRDs under treatment with JAK-i, and to identify factors that might be associated with reduced immunogenicity, and therefore reduced protection. Methods We investigated humoral and cellular CD4 and CD8 immune responses following a two-dose regimen of the recombinant inactive vaccine in 43 patients with rheumatic diseases treated with different JAK-i. The responses were compared with age, gender and disease-matched healthy controls. Results Patients with IMRDs treated with JAK-i showed reduced seroconversion rate (63% vs. 100% and lower VZV IgG titres (1222 ± 411 vs. 3048 ± 556, P < 0.0001) as compared with healthy controls. Functional T CD4 (IL-2 plus IFN-γ secretion) and T CD8 (granzyme A and/or granzyme B secretion) immune responses were also significantly diminished in IMRD patients. Negative correlation was found between VZV antibody titres and age, specific treatments (baricitinib, tofacitinib, upadacitinib), cumulative MTX and glucocorticoid doses, history of multiple DMARDs and treatment duration with JAK-i. Functional T-CD4 responses but not functional T-CD8 responses also showed similar negative correlations. Positive associations were observed between functional T-CD4 and T-CD8 responses. Conclusions Our study provides valuable insights into the immune responses elicited by the recombinant inactive vaccine in patients with IMRDs treated with JAK-i. In these patients we have observed a broad impact on the adaptive humoral and cellular immune responses, suggesting a potential reduction in protection against HZ infection and VZV reactivation.