Evaluation of Varicella‐zoster virus‐specific cell‐mediated immunity by interferon‐γ Enzyme‐Linked Immunosorbent Assay in adults ≥50 years of age administered a herpes zoster vaccine

Abstract

Varicella‐zoster virus (VZV)‐specific cell‐mediated immunity (CMI) is critical for preventing and controlling the onset of herpes zoster (HZ). To assess VZV CMI, an interferon‐γ (IFN‐γ) enzyme‐linked immunosorbent assay (ELISA) was validated by examining the influence of VZV‐specific antigen content, incubation time, and interval from whole blood collection on the assay. In phase II clinical trial, VZV‐specific CMI in adults ≥50 years of age administered an HZ vaccine were evaluated by IFN‐γ ELISA, as determined by measuring IFN‐γ production in the whole blood in response to stimulation with ultraviolet light‐inactivated VZV. The VZV‐specific IFN‐γ levels varied among individuals from prevaccination (baseline) to 6 weeks postvaccination. In most subjects, VZV‐specific CMI was increased at 6 weeks postvaccination. The HZ vaccine elicited a significant increase in the VZV‐specific CMI response as measured by ELISA; the geometric mean fold‐rises from baseline to 6 weeks postvaccination were 3.50, 4.22, and 5.24 in the 4.3, 4.7, and 4.9 log plaque‐forming unit vaccine groups, respectively, which was significantly higher than in the placebo group (P < 0.05). These results indicate that vaccination enhances the VZV‐specific CMI responses in subjects; IFN‐γ ELISA is an effective method for evaluating the CMI response and may be useful for identifying individuals at a high risk of HZ infection.

A Simple-to-Perform ifn-γ mRNA Gene Expression Assay on Whole Blood Accurately Appraises Varicella Zoster Virus-Specific Cell-Mediated Immunity After Allogeneic Hematopoietic Stem Cell Transplantation

“…Consistently, 29/42 (69%) of VZV non-responders had positive VZV IgG values in this study. Different IFA have been proposed to quantify VZV-specific cell-mediated immunity, but there is no validated “gold standard.” VZV-specific T-cell proliferation assays, performed on PBMC or whole blood ( 5 , 20 , 22 , 36 , 37 ), have several limitations. The first relates to the various origins of IFN-γ production.…”

“…HI (n = 17) and allo-HSCT recipients (n = 60) were included. HI and allo-HSCT recipients did not significantly differ in terms of age (median [IQR], 42 [33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] vs. 44.5 years, P = .39) and sex (sex ratio, 1.1 vs. 1.3, P = .79). Allo-HSCT recipients were enrolled at a median [IQR] time of 6 [5][6][7][8] months posttransplant.…”

Photoactivatable Aptamer-CRISPR Nanodevice Enables Precise Profiling of Interferon-Gamma Release in Humanized Mice

“…5−7 Various enzyme-linked immunosorbent assays have been developed to measure the circulating IFN-γ from liquid biopsies such as blood. 8,9 However, accumulating evidence indicates that circulating IFN-γ concentrations may differ from concentrations in TME and thus inaccurately reflect the cytokine dynamics within the tumor. 10,11 Furthermore, recent studies suggest that the dynamics of intratumoral IFN-γ differentially impacts on tumors upon ICB.…”

“…Immune checkpoint blockade (ICB) therapy, which aims to harness the immune system to fight cancer, has emerged as a promising therapeutic strategy. , However, the clinical efficacy of ICB therapy is often limited by the complexity of the immune response and the heterogeneity of the tumor microenvironment (TME). To better understand and optimize ICB, researchers have investigated the role of peripheral blood lymphocytes and related cytokines in evaluating immune responses. , For instance, interferon-gamma (IFN-γ), a key cytokine predominantly produced by activated T cells or cytotoxic T lymphocytes (CTLs), has been considered as an attractive biomarker for effective immunoactivation. − Various enzyme-linked immunosorbent assays have been developed to measure the circulating IFN-γ from liquid biopsies such as blood. , However, accumulating evidence indicates that circulating IFN-γ concentrations may differ from concentrations in TME and thus inaccurately reflect the cytokine dynamics within the tumor. , Furthermore, recent studies suggest that the dynamics of intratumoral IFN-γ differentially impacts on tumors upon ICB. , Thus, histological analysis of tumor tissue biopsy is an alternative way to determine IFN-γ within the tumor, but this requires invasive sampling and is a snapshot assay that can only reflect regional IFN-γ at a specific time point. , Therefore, there is an unmet need to visualize intratumoral IFN-γ in real time, which can provide accurate predictions of the dynamic immune reactivity during ICB therapy.…”