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In this trial of a recombinant VZV glycoprotein E subunit vaccine with the adjuvant AS01 B , the risk of herpes zoster and postherpetic neuralgia is shown to be significantly lower in association with the vaccine than with placebo among persons 70 years of age or older. Herpes zoster, or shingles, results from the reactivation of latent varicella–zoster virus (VZV) and typically manifests as a vesicular, painful dermatomal rash. 1 , 2 The most common complication of herpes zoster, postherpetic neuralgia, manifests as chronic neuropathic pain that can greatly limit daily activities. 1 , 3 – 6 The overall incidence of herpes zoster is 2.0 to 4.6 cases per 1000 person-years but increases with age to 10.0 to 12.8 per 1000 person-years among persons 80 years of age or older. 7 – 10 Similarly, the incidence of postherpetic neuralgia also increases with age. 10 – 13 Antiviral therapy can reduce the duration of herpes zoster rash . . .

In this randomized, controlled trial involving more than 15,000 participants 50 years of age or older, a varicella–zoster virus subunit vaccine with AS01B adjuvant was found to have an efficacy of more than 96% in preventing herpes zoster. Herpes zoster, or shingles, results from the reactivation of latent varicella–zoster virus (VZV) in the dorsal-root or cranial-nerve ganglia, usually decades after primary infection. 1 , 2 Herpes zoster is characterized by a vesicular rash with a unilateral and dermatomal distribution and is almost always accompanied by pain. More than 90% of adults have been infected with VZV and are at risk for herpes zoster. 3 , 4 Although herpes zoster is most frequent in adults who are 50 years of age or older owing to immunosenescence, it can occur at any age, especially when cell-mediated immunity is decreased as a result of disease . . .

The adjuvanted varicella-zoster virus (VZV) glycoprotein E (gE) subunit herpes zoster vaccine (HZ/su) confers higher protection against HZ than the live attenuated zoster vaccine (ZV). To understand the immunologic basis for the different efficacies of the vaccines, we compared immune responses to the vaccines in adults 50 to 85 years old. gE-specific T cells were very low/undetectable before vaccination when analyzed by FluoroSpot and flow cytometry. Both ZV and HZ/su increased gE-specific responses, but at peak memory response (PMR) after vaccination (30 days after ZV or after the second dose of HZ/su), gE-specific CD4+ and CD8+ T cell responses were 10-fold or more higher in HZ/su compared with ZV recipients. Comparing the vaccines, T cell memory responses, including gE-IL-2+ and VZV-IL-2+ spot-forming cells (SFCs), were higher in HZ/su recipients and cytotoxic and effector responses were lower. At 1 year after vaccination, all gE-Th1 and VZV-IL-2+ SFCs remained higher in HZ/su compared with ZV recipients. Mediation analyses showed that IL-2+ PMR were necessary for the persistence of Th1 responses to either vaccine and VZV-IL-2+ PMR explained 73% of the total effect of HZ/su on persistence. This emphasizes the biological importance of the memory responses, which were clearly superior in HZ/su compared with ZV participants.

Background. The Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Study 403) demonstrated that zoster vaccine was efficacious through 4 years after vaccination. The Short-Term Persistence Substudy (STPS) was initiated after the SPS to further assess the persistence of vaccine efficacy. Methods. The STPS re-enrolled 7320 vaccine and 6950 placebo recipients from the 38 546-subject SPS population. Methods of surveillance, case determination, and follow-up were analogous to those in the SPS. Vaccine efficacy for herpes zoster (HZ) burden of illness, incidence of postherpetic neuralgia (PHN), and incidence of HZ were assessed for the STPS population, for the combined SPS and STPS populations, and for each year through year 7 after vaccination. Results. In the STPS as compared to the SPS, vaccine efficacy for HZ burden of illness decreased from 61.1% to 50.1%, vaccine efficacy for the incidence of PHN decreased from 66.5% to 60.1%, and vaccine efficacy for the incidence of HZ decreased from 51.3% to 39.6%, although the differences were not statistically significant. Analysis of vaccine efficacy in each year after vaccination for all 3 outcomes showed a decrease in vaccine efficacy after year 1, with a further decline thereafter. Vaccine efficacy was statistically significant for the incidence of HZ and the HZ burden of illness through year 5. Conclusions. Vaccine efficacy for each study outcome was lower in the STPS than in the SPS. There is evidence of the persistence of vaccine efficacy through year 5 after vaccination but, vaccine efficacy is uncertain beyond that point.

Background. Human immunodeficiency virus (HIV)-infected individuals are at increased risk of herpes zoster (HZ), even in the antiretroviral therapy (ART) era. Because concerns exist about the use of live-attenuated vaccines in immunocompromised individuals, a subunit vaccine may be an appropriate alternative. Methods. This phase 1/2, randomized, placebo-controlled study evaluated the immunogenicity and safety of an investigational HZ subunit vaccine (HZ/su). Three cohorts of HIV-infected adults aged ≥18 years were enrolled: 94 ART recipients with a CD4⁺ T-cell count of ≥200 cells/mm³, 14 ART recipients with a CD4⁺ T-cell count of 50-199 cells/mm³, and 15 ART-naive adults with a CD4⁺ T-cell count of ≥500 cells/mm³. Subjects received 3 doses of HZ/su (50 μg varicella-zoster virus glycoprotein E [gE] combined with AS01B adjuvant) or 3 doses of saline at months 0, 2, and 6. Results. One month after dose 3, serum anti-gE antibody concentrations and frequencies of gE-specific CD4⁺ T cells were higher following HZ/su vaccination than after receipt of saline (P<.0001). Median cell-mediated immune responses peaked after dose 2. Humoral and cell-mediated immune responses persisted until the end of the study (month 18). No vaccination-related serious adverse events were reported. No sustained impact on HIV load or CD4⁺ T-cell count was noted following vaccinations. Conclusions. HZ/su was immunogenic and had a clinically acceptable safety profile in HIV-infected adults. Clinical Trials Registration. NCT01165203

The licensed adjuvanted recombinant glycoprotein E (gE) subunit vaccine (HZ/su) is highly effective against herpes zoster (HZ). This randomised, active-controlled, non-inferiority trial (ChiCTR2300079076) compared the immunogenicity and safety of a novel gE-Fc fusion protein vaccine candidate (LZ901) with HZ/su in 300 healthy adults aged ≥50 years without prior HZ vaccination in Wuxi, China. Participants received either two doses of LZ901 (30-day interval; n = 151) or HZ/su (60-day interval; n = 149). The primary outcomes was the proportion of participants with simultaneous positive responses to two or more cytokines (IFN-γ, IL-2, TNF-α, or CD40L) 30 days after the second dose (referred to as gE-specific CD4 2+ /CD8 2+ T-cell responses). LZ901 demonstrated non-inferiority to HZ/su (margin > −10%) for both CD4 + and CD8 + T-cell responses. Significantly higher response rates were observed with LZ901 for CD4 2  + T-cell responses (83.0% [117/141] vs 58.1% [79/136]; p < 0.0001) and CD8 2  + T-cell responses (46.8% [66/141] vs 8.8% [12/136]; p < 0.0001). Adverse reactions were markedly lower with LZ901 (41.1% [62/151] vs 87.9% [131/149]; p < 0.0001), including grade 3 events (0.7% [1/151] vs 6.0% [9/149]). LZ901 induced superior cellular immunogenicity and exhibited a better safety profile than HZ/su in adults ≥50 years, supporting its potential as a promising HZ prevention candidate vaccine. In this clinical trial, the authors demonstrate that recombinant gE-Fc Fusion Protein Vaccine LZ901 for herpes zoster induces superior cellular immunogenicity and exhibits a better safety profile than HZ/su in adults ≥50 years, supporting its potential as vaccine candidate.

BackgroundA double-blind, placebo-controlled trial that involved 38,546 subjects ⩾60 years old demonstrated efficacy of a high-potency live-attenuated Oka/Merck varicella-zoster virus (VZV) vaccine. The trial included an immunology substudy to determine the relationship of VZV-specific immune responses to vaccination and clinical outcome MethodsThe immunology substudy enrolled 1395 subjects at 2 sites where blood samples obtained prior to vaccination, at 6 weeks after vaccination, and at 1, 2, and 3 years thereafter were tested for VZV-specific cell-mediated immunity (VZV-CMI) by γ-interferon ELISPOT and responder cell frequency assays and for VZV antibody by glycoprotein ELISA ResultsVZV-CMI and VZV antibodies were significantly increased in vaccine recipients at 6 weeks after vaccination. The vaccine-induced increases in VZV-CMI persisted during the 3 years of follow-up, although their magnitude decreased over time. The magnitude of these VZV-specific immune responses was greater in subjects 60–69 years old than in subjects ⩾70 years old ConclusionsThe zoster vaccine induced a significant increase in VZV-CMI and VZV antibody. The magnitude and duration of the boost in VZV-CMI in vaccine recipients and the relationship of this boost to age paralleled the clinical effects of the vaccine observed during the efficacy trial. These findings support the hypothesis that boosting VZV-CMI protects older adults against herpes zoster and postherpetic neuralgia

When the adjuvanted HZ subunit vaccine candidate was coadministered with a quadrivalent seasonal influenza vaccine, no interference in the immune responses were observed, and no safety concerns were identified. Abstract Background The immunogenicity and safety of an adjuvanted herpes zoster subunit (HZ/su) vaccine when coadministered with a quadrivalent seasonal inactivated influenza vaccine (IIV4) was investigated in a phase 3, open-label, randomized clinical trial in adults aged ≥50 years. Methods Subjects were randomized 1:1 to receive either HZ/su (varicella zoster virus glycoprotein E; AS01B Adjuvant System) and IIV4 at day 0 followed by a second HZ/su dose at month 2 (coadministration group), or IIV4 at month 0 and HZ/su at months 2 and 4 (control group). The primary objectives were the HZ/su vaccine response rate in the coadministration group and the noninferiority of the antibody responses to HZ/su and IIV4 in the coadministration compared with the control group. Safety information was collected throughout the duration of the study. Results A total of 413 subjects were vaccinated in the coadministration group and 415 in the control group. The HZ/su vaccine response rate in the coadministration group was 95.8% (95% confidence interval, 93.3%–97.6%) and the anti–glycoprotein E GMCControl/Coadmin ratio was 1.08 (.97–1.20). The primary noninferiority objectives were met. No safety concerns were observed. Conclusions No interference in the immune responses to either vaccine was observed when the vaccines were coadministered, and no safety concerns were identified. Clinical Trials Registration NCT01954251.

Reactivation of latent varicella-zoster virus can cause herpes zoster (shingles) and associated complications, such as post-herpetic neuralgia. The adjuvanted recombinant zoster vaccine (RZV) was shown to be efficacious in preventing herpes zoster and have an acceptable safety profile in adults ≥50 years of age. However, no clinical data on RZV were available in an Indian population. The aim of the current study was to assess the immunogenicity and safety of RZV in adults ≥50 years of age in India. In this randomized, placebo-controlled, observer-blind, multi-center trial, conducted between February 2022 and March 2023, participants ≥50 years of age received two doses (with a two-month interval) of RZV (N = 143) or placebo (N = 145). Blood samples were collected pre-dose 1 and one month post-dose 2 to quantify anti-glycoprotein E (gE) antibody concentrations. Solicited adverse events (AEs) with onset within seven days and unsolicited AEs with onset within 30 days following any RZV or placebo dose were recorded. Serious AEs (SAEs) and potential immune-mediated diseases (pIMDs) were recorded until trial end (six months post-dose 2). At one month post-dose 2, vaccine response rate in the RZV group was 85.7 % (95 % confidence interval [CI]: 78.4 %–91.3 %), meeting the primary objective's success criterion (lower limit of 95 % CI ≥60 %). The adjusted geometric mean anti-gE antibody concentration ratio between the RZV and placebo groups was 19.8 (95 % CI, 14.1–27.8), meeting the secondary objective's success criterion (lower limit of 95 % CI ≥3). Solicited AEs were reported by 103 (72.0 %) RZV and 86 (59.3 %) placebo recipients; most had mild-to-moderate severity. No intervention-related unsolicited AE or SAE and no pIMD or death were reported. Two doses of RZV induced a robust antibody response, comparable to that reported in other populations, and had a safety profile similar to the known RZV safety profile. ClinicalTrials.gov: NCT05219253 •The immunogenicity and safety of recombinant zoster vaccine (RZV) were evaluated in adults ≥50 years old in India.•Two doses of RZV induced a robust humoral immune response in this population.•The safety profile in Indian adults ≥50 years old was consistent with RZV's known safety profile.

Background. Herpes zoster vaccine (ZV) was administered as a second dose to 200 participants ≥70 years old who had received a dose of ZV ≥10 years previously (NCT01245751). Methods. Varicella zoster virus (VZV) antibody titers (measured by a VZV glycoprotein-based enzyme-linked immunosorbent assay [gpELISA]) and levels of interferon γ(IFN-γ) and interleukin 2 (IL-2; markers of VZV-specific cell-mediated immunity [CMI], measured by means of ELISPOT analysis) in individuals aged ≥70 years who received a booster dose of ZV were compared to responses of 100 participants aged 50-59 years, 100 aged 60-69 years, and 200 aged ≥70 years who received their first dose of ZV. The study was powered to demonstrate noninferiority of the VZV antibody response at 6 weeks in the booster-dose group, compared with the age-matched first-dose group. Results. Antibody responses were similar at baseline and after vaccination across all age and treatment groups. Both baseline and postvaccination VZV-specific CMI were lower in the older age groups. Peak gpELISA titers and their fold rise from baseline generally correlated with higher baseline and postvaccination VZV-specific CMI. IFN-γ and IL-2 results for subjects ≥70 years old were significantly higher at baseline and after vaccination in the booster-dose group, compared with the first-dose group, indicating that a residual effect of ZV on VZV-specific CMI persisted for ≥10 years and was enhanced by the booster dose. Conclusions. These findings support further investigation of ZV administration in early versus later age and of booster doses for elderly individuals at an appropriate interval after initial immunization against HZ. Clinical Trials Registration. NCT01245751.