P-203 Varicella Zoster virus vaccination in immunocompromised patients with haematological and rheumatological diseases: specific T-cell response measured with an in-house interferon gamma release assay

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Background The reactivation of varicella-zoster virus (VZV) causes herpes zoster (HZ). VZV-specific T-cell -mediated immunity (CMI) is considered fundamental to prevent HZ. Age and immunomodulating drugs can impair VZV-specific CMI and contribute to HZ occurrence. A new adjuvanted recombinant subunit vaccine (HZ/su) has been recently approved for the prevention of HZ in adults with immunosuppression. Our study aimed to investigate VZV-specific immunity in haematological (HE) and rheumatological (RH) patients under immune modulating treatments or chemotherapy after HZ/su vaccination. Material and Methods HE and RH patients under active treatments were enrolled in the study. Two doses of HZ/su were administered 1 month apart (T0 and T1 respectively), with a follow-up visit 1 month after the second dose (T2). T-cell responses were assessed at T0 and T2 with an in-house Interferon Gamma Release Assay (IGRA), consisting of heparin whole blood stimulation with VZV gE and Immediate Early (IE)-63 peptide libraries. Each test included a negative (NC) and positive (phytohemagglutinin, PHA) control. IFN-gamma production was measured with the automated ELLA platform. Data were represented as median (interquartile range, IQR). Medians were compared using the non-parametric Wilcoxon matched-pairs signed rank test. Results We enrolled 19 patients (14F/15M) with severe immunodeficiency who completed the vaccination schedule and with at least 1 month of follow up after the second dose. 13 (68%) had HE disease (2 multiple myeloma [MM], 11 B-cell lymphoma [BCL]); 6 (32%) had RH disease (all with rheumatoid arthritis) under corticosteroid and Jak-2 inhibitors treatment. Median age was 63 years (IQR 56–71). All patients were under active treatments. Median IFN-gamma production after gE stimulation was 1.1 pg/ml, and 46.7 pg/ml at T0 and T2, respectively (Wilcoxon p<0.001). Median IFN-gamma production after IE-63 stimulation was 1.3 pg/ml, and 1.1 pg/ml at T0 and T2, respectively (Wilcoxon p=0.1) (figure 1). An effective vaccinal response was defined as a 4-fold increase in IFN-gamma production in the gE stimulated condition, from T0 to T2. 5/19 (26%) patients were considered as non-responder (all of them with HE malignancy, 1 MM and 4 BCL) Conclusions VZV gE IGRA is a sensitive and specific tool to assess CMI after HZ/su vaccination in HE and RH patients. HZ/su elicited a significant T-cell response in all patients with RH diseases and in more than 60% of patients with HE malignancy. However, 5 patients had a limited or absent increase of IFN-gamma production from T0 to T2. This aspect highlights the importance of assessing VZV-specific after HZ/su vaccination CMI in patients with HE malignancy receiving immune modulating treatments or chemotherapies to verify protection from VZV reactivation and HZ development.

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