Impaired cellular immune responses to herpes zoster subunit vaccine in patients with rheumatoid arthritis receiving Janus kinase inhibitors

Abstract Objective To investigate cellular immune responses to the herpes zoster (HZ) subunit (HZ/su) vaccine in patients with rheumatoid arthritis (RA) treated with Janus kinase inhibitors (JAKis). Methods RA patients treated with JAKi (n = 46) at the Department of Rheumatology, Skåne University Hospital, Sweden, and healthy controls (n = 37) received two doses of the HZ/su vaccine. Blood samples were collected before and ∼6 weeks after vaccination. Varicella zoster virus (VZV) glycoprotein E (gE)-specific lymphocyte proliferation was analysed using flow cytometry. gE-specific production of tumour necrosis factor (TNF)α and IFNγ was analysed using an immunoassay. gE-specific responses were compared before and after vaccination within the groups (Wilcoxon signed-rank test), and between the patients and the controls (Mann–Whitney, ANCOVA). Proportions achieving a positive vaccine response were compared between the groups (Chi2 test). Results Following vaccination, gE-specific proliferation of CD19+ cells increased significantly in both the patients (P = 0.016) and the controls (P < 0.001). For patients, no statistically significant differences were seen after vaccination for gE-specific proliferation of CD4+ or CD8+ cells or production of TNFα or IFNγ. Lower proportions of patients than the controls achieved a positive vaccine response for gE-specific proliferation of CD4+, CD8+ and CD19+ cells and gE-specific TNFα. Conclusion The lack of significant increases in both vaccine-specific proliferation of CD4+ and CD8+ cells and proinflammatory cytokines after vaccination indicate impaired T cell responses to the HZ/su vaccination in patients with RA treated with JAKi. These results suggest that to ensure satisfactory cellular immunity in patients with RA, vaccination against HZ should preferably be performed before the initiation of JAKi treatment. Clinical Trial Registration ClinicalTrials.gov; NCT03886038