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Background In phase 3 trials, inactivated varicella zoster virus (VZV) vaccine (ZVIN) was well tolerated and efficacious against herpes zoster (HZ) in autologous hematopoietic stem cell transplant (auto-HSCT) recipients and patients with solid tumor malignancies receiving chemotherapy (STMc) but did not reduce HZ incidence in patients with hematologic malignancies (HMs). Here, we describe ZVIN immunogenicity from these studies. Methods Patients were randomized to ZVIN or placebo (4 doses). Immunogenicity was assessed by glycoprotein enzyme-linked immunosorbent assay (gpELISA) and VZV interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay in patients receiving all 4 doses without developing HZ at the time of blood sampling. Results Estimated geometric mean fold rise ratios (ZVIN/placebo) by gpELISA and IFN-y ELISPOT ~28 days post–dose 4 were 2.02 (95% confidence interval [CI], 1.53–2.67) and 5.41 (95% CI, 3.60–8.12) in auto-HSCT recipients; 1.88 (95% CI, 1.79–1.98) and 2.10 (95% CI, 1.69–2.62) in patients with STMc; and not assessed and 2.35 (95% CI, 1.81–3.05) in patients with HM. Conclusions ZVIN immunogenicity was directionally consistent with clinical efficacy in auto-HSCT recipients and patients with STMc even though HZ protection and VZV immunity were not statistically correlated. Despite a lack of clinical efficacy in patients with HM, ZVIN immunogenicity was observed in this population. Immunological results did not predict vaccine efficacy in these 3 populations. Clinical trial registration NCT01229267, NCT01254630. [ABSTRACT FROM AUTHOR]

Older age is associated with increased infectious morbidity and decreased immune responses to vaccines, but the mechanisms that mediate this effect are incompletely understood. The efficacy and immunogenicity of live attenuated zoster vaccine (ZVL) have a very well described negative association with the age of the vaccinee. In a study of 600 ZVL recipients 50 to >80 years of age, we investigated immunologic factors that might explain the effect of age on the immunogenicity of ZVL. Using FluoroSpot and flow cytometry, we determined that varicella-zoster virus (VZV)-specific peak Th1 (VZV-Th1) responses to ZVL were independently predicted by pre-vaccination VZV-Th1 responses, regulatory T cells (Treg) and PD1-expressing Tcheck, but not by age of the vaccinee. Persistence of VZV-Th1 at 1 year after vaccination was independently predicted by the factors above and by peak VZV Th1 responses to ZVL and age of the vaccinee. We further demonstrated by ex-vivo blocking experiments the mechanistic role of PD1 and CTLA4 as modulators of decreased VZV-Th1 responses in the study participants. VZV-specific cytotoxic T cell (VZV-CTL) and T follicular helper responses to ZVL did not correlate with age, but similar to other Th1 responses, VZV-CTL peak and baseline responses were independently correlated. These data expand our understanding of the factors affecting the magnitude and kinetics of T cell responses to ZVL in older adults and show the importance of pre-vaccination Treg and Tcheck in modulating the immunogenicity of ZVL. This presents new potential interventions to increase vaccine responses in older adults. [ABSTRACT FROM AUTHOR]