Immunogenicity, Efficacy and Safety of Recombinant Herpes Zoster Vaccine in Frail Patients

Herpes zoster (HZ) is a serious health problem whose incidence and severity increase with the decline of cell-mediated immunity (CMI) because of age and immunocompromised (IC) status. Subclinical reactivation are described and may boost the adaptive specific immunity. T cells play a major role in preventing reactivation of Varicella Zoster virus (VZV), with a contribution of both CD4 and CD8 T cells. Accordingly, the suppression of VZV-specific T cells preceded the occurrence of HZ. Moreover, several observations support a role of B cells in contributing to the overall protection against HZ as patients with primary antibody deficiency, common variable immunodeficiency, or patients treated with B-cell depleting therapies or Janus Kinase inhibitors (JAKis) show a higher risk of HZ. The functional effectiveness of CMI can be significantly affected by different diseases (e.g. cancer and immune-mediated inflammatory diseases, IMIDs) and/or by ongoing immune-targeted therapy, giving these patients at high risk for VZV reactivation. The new recombinant zoster vaccine (RZV) reduces the risk of HZ, and vaccination is encouraged in IC individuals, including those with cancer and IMIDs. Despite the efficacy and safety of RZV in healthy adults, data on IC patients are scarce. In particular, the immunogenicity of the new vaccine in frail subjects is not fully understood. On the one hand, immunosuppressive treatments can compromise the residual immunity to VZV but also the response to RZ . Several therapies are known to affect B cell response such as Rituximab or CAR T cells; other treatments reduce the T cell functionality, such as T-cell inhibitors (Cytotoxic T-lymphocyte Antigen 4-Immunoglobulin, CTLA4-Ig; abatacept), the JAK is, as well as by chemotherapy. To date, the vaccination is not approved in paediatric patients. However, the investigation of the VZV-specific immunological profile in frail paediatric patients could represent a valuable tool for understanding the potential vaccination strategies in these categories.

The study and definition of an immune profile associated with a high risk of viral in RZV vaccinated patients with IC can be useful for identifying patients' candidates for preventive antiviral treatments.

This is an observational multicentric prospective cohort study. The general objective is to assess the immunogenicity of RZV vaccination in terms of the induction of humoral and cell-mediated immune responses in selected frail (altered immunocompetence) populations, including rheumatologic, oncologic, neurologic and hematologic patients.

Primary Objective: To define the overall rate of humoral responders patients after the second dose of RZV administration.

Primary Endpoint: The rate of "humoral responders" will be defined as the percentage of patients showing ≥ 4 times of gE-specific IgG response (IU/mL) after the second dose (T1m) respect to baseline (T0) Secondary Objective 2.1: To define the overall increase of humoral response after the second dose of RZV administration.

Secondary Objective 2.2: To characterize the immunogenicity induced by RZV vaccine in the different study cohorts (rheumatologic, oncologic, neurologic and hematologic patients) Secondary Objective 2.3: To evaluate the kinetics of humoral response during the first year after the vaccination Secondary Objective 2.4: To characterize gE-specific T cell mediated response elicited by RZV vaccination in overall patients Secondary Objective 2.5: Evaluation of the incidence of adverse reactions (AR) to the RZV vaccine, local and systemic, solicited and unsolicited, within the period of four weeks after the second dose of RZV.

Secondary Objective 2.6: Evaluation of the incidence of reactivation of VZV cases after the second dose of RZV.