Background/Purpose: Patients with immune-mediated rheumatic diseases treated with JAK inhibitors face an elevated risk of herpes zoster (HZ) infection. Shingrix, a recombinant inactive vaccine, offers protection against HZ. However, limited data exist on Shingrix vaccine responses in patients with immune-mediated rheumatic diseases (IMRD). We aim to characterize B-cell and T-cell immune responses elicited by the HZ recombinant subunit vaccine in patients with IMRDs under treatment with JAK inhibitors, 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 inhibitors. The responses were compared with age, gender and disease-matched healthy controls.

Results: Patients with IMRDs treated with JAK inhibitors showed reduced seroconversion rate (63% vs 100% and lower VZV IgG titers (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 IMRDs patients.  Negative correlation was found between VZV antibody titers and age, specific treatments (baricitinib, tofacitinib, upadacitinib), cumulative methotrexate and glucocorticoid doses, history of multiple DMARDs, and treatment duration with JAK inhibitors. 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.

Conclusion: Our study provides valuable insights into the immune responses elicited by the recombinant inactive vaccine in patients with IMRDs treated with JAK inhibitors. In these patients we have observed a broad impact on the adaptive humoral and cellular immune responses, suggesting a potential reduction in protection against herpes zoster infection and VHZ reactivation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/immune-responses-to-herpes-zoster-vaccine-responses-in-rheumatic-patients-on-jak-inhibitors-insights-in-humoral-and-cellular-response/