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The burden of herpes zoster (HZ) is recognized worldwide; however, there is seemingly limited information on incidence and vaccination practices in Southeast Asia (SEA). A scientific workshop was held by the Zoster Experts' Network to exchange and consolidate insights on the burden of HZ and the patient pathway in SEA. The workshop included practicing clinical experts and public health specialists/epidemiologists from Indonesia, Malaysia, the Philippines, Thailand, and Vietnam. It aimed to identify gaps in the literature, outline patient pathways, and evaluate HZ vaccine recommendations among these countries. Consensus was identified on the substantial lack of epidemiological data on HZ in SEA and the need to investigate the impact of age, immunocompromising conditions, and comorbidities on the incidence and severity of HZ in the region. However, available data in SEA did indicate a rising disease and socioeconomic burden of HZ, with concerns that current treatment strategies for HZ are suboptimal. The HZ patient pathways generated by the experts highlighted common themes and differences between the five countries. Furthermore, the experts highlighted the lack of awareness of HZ and its impact on patients' quality of life, among patients and healthcare professionals. Evaluation of the current local HZ vaccine recommendations further showed differences in age and the inclusion of at-risk populations between countries. The workshop outcomes emphasize the need for further HZ surveillance in SEA. Efforts to align and address leakage within the patient pathway and raise awareness on the impact of HZ should be prioritized. Awareness initiatives and alignment on vaccine recommendations are also needed. [ABSTRACT FROM AUTHOR]

The burden of herpes zoster (HZ) is recognized worldwide; however, there is seemingly limited information on incidence and vaccination practices in Southeast Asia (SEA). A scientific workshop was held by the Zoster Experts’ Network to exchange and consolidate insights on the burden of HZ and the patient pathway in SEA. The workshop included practicing clinical experts and public health specialists/epidemiologists from Indonesia, Malaysia, the Philippines, Thailand, and Vietnam. It aimed to identify gaps in the literature, outline patient pathways, and evaluate HZ vaccine recommendations among these countries. Consensus was identified on the substantial lack of epidemiological data on HZ in SEA and the need to investigate the impact of age, immunocompromising conditions, and comorbidities on the incidence and severity of HZ in the region. However, available data in SEA did indicate a rising disease and socioeconomic burden of HZ, with concerns that current treatment strategies for HZ are suboptimal. The HZ patient pathways generated by the experts highlighted common themes and differences between the five countries. Furthermore, the experts highlighted the lack of awareness of HZ and its impact on patients’ quality of life, among patients and healthcare professionals. Evaluation of the current local HZ vaccine recommendations further showed differences in age and the inclusion of at-risk populations between countries. The workshop outcomes emphasize the need for further HZ surveillance in SEA. Efforts to align and address leakage within the patient pathway and raise awareness on the impact of HZ should be prioritized. Awareness initiatives and alignment on vaccine recommendations are also needed.

Kidney transplant (KT) recipients have an increased risk of herpes zoster (HZ) and its complications. Although recombinant zoster vaccine is favoured over zoster vaccine live (ZVL), ZVL is also recommended to prevent HZ for KT candidates. We aimed to evaluate the clinical effectiveness of ZVL in KT recipients immunized before transplantation. Adult patients who received kidney transplantation from January 2014 to December 2018 were enrolled. Patients were observed until HZ occurrence, death, loss of allograft, loss to follow-up, or 5 years after transplantation. The inverse probability of the treatment-weighted Cox proportional hazard model was used to compare the incidence of HZ after transplantation between vaccinated and unvaccinated patients. A total of 84 vaccinated and 340 unvaccinated patients were included. The median age was higher in the vaccinated group (57 vs. 54 years, p 0.003). Grafts from deceased donors were more frequently transplanted in the unvaccinated group (16.7% vs. 51.8%, p < 0.001). Five-year cumulative HZ incidence was 11.9%, which translated to 26.27 (95% CI, 19.33–34.95) per 1000 person-years. The incidence in the vaccinated and unvaccinated groups was 3.9% and 13.7%, respectively. After adjustment, vaccination showed significant protective effectiveness against HZ (adjusted hazard ratio, 0.18, 95% CI, 0.05–0.60). In addition, all four cases of disseminated zoster occurred in the unvaccinated group. Our study, the first on the clinical effectiveness of zoster vaccines for KT recipients, suggests that ZVL before transplantation effectively prevents HZ. [ABSTRACT FROM AUTHOR]

Although 1 in 3 people globally are expected to develop herpes zoster (HZ; i.e. shingles), HZ vaccination is not currently part of the Philippine National Immunization Program and HZ is not considered as one of the main vaccine-preventable diseases highlighted by the Department of Health. We report the findings from two advisory boards held with healthcare professionals (HCPs) to understand the current landscape of HZ management and prevention in the Philippines. The first advisory board focused on the management and prevention of HZ in patients aged ≥50 years, the second in immunocompromised patients aged ≥18 years. HCPs reported seeing HZ cases across specialties, with the most common complication being postherpetic neuralgia. HZ was reported to impose a substantial burden on patients, due to both the cost of treatment and distress caused due to pain. HZ could also complicate the treatment of ongoing conditions. HCPs agreed that the introduction of the recombinant zoster vaccine, which was recently approved by the Philippines Food and Drug Administration, could help in the prevention of HZ, addressing the needs of both HCPs and patients. Suggested steps to establish HZ vaccination in the Philippines included improved HCP and patient education, and establishing local HZ vaccine recommendations.

Objective: To investigate the efficacy, effectiveness and safety of recombinant zoster vaccine (RZV) and zoster vaccine live (ZVL) in immunocompetent and immunocompromised subjects. Methods: Data sources: PubMed, EMBASE, Cochrane Library, and Web of Science databases (up to Jan 2022) were searched to identify English articles. Search terms included randomized controlled trials (RCTs), observational studies, herpes zoster, RZV, ZVL. Study Selection: Only randomized controlled trials (RCTs) evaluating vaccine efficacy and safety and observational studies assessing vaccine effectiveness (after a vaccine was approved for marketing) were included. Data Extraction: Two researchers independently screened the literature, extracted the data, and checked the each other results. Results: Seventeen RCTs and 19 cohort studies were included. Among immunocompetent subjects, RZV was superior to ZVL at wide intervals (relative vaccine efficacy: 84%, 95% CI: 53%-95%; relative vaccine effectiveness: 49%, 95% CI: 21%-67%), across genders and subjects aged = 60 years. Among immunocompromised subjects, RZV was superior to placebo in terms of vaccine efficacy (60%, 95% CI: 49%-69%). There was no difference between ZVL and placebo in those with selected immunosuppressive conditions. RZV was 45% (95% CI: 30%-59%) superior to ZVL in real-world practice. Compared with placebo, adverse events related to RZV were primarily related to injection-site and systemic, and RZV did not increase the risk of serious adverse events (SAEs) or death. There was no difference in the incidence of adverse events between groups with and without immunosuppression. Conclusions: Both RZV and ZVL can reduce the risk of herpes zoster in both immunocompetent and immunocompromised subjects. RZV was well-tolerated in the study population and demonstrated stronger protection than ZVL. [ABSTRACT FROM AUTHOR]

We compared glycoprotein E (gE)- and varicella zoster virus (VZV)-specific Th1 immunity in 160 adults, aged 50-85 years, randomized to receive live or recombinant zoster vaccine (RZV). gE-specific responses measured by interferon-γ (IFN-γ) and interleukin 2 (IL-2) dual-color Fluorospot were significantly higher at all time points postimmunization in RZV recipients. VZV-specific IL-2+ memory, but not IFN-γ+ or IFN-γ+IL-2+ effector responses, were higher in RZV recipients at ≥3 months postimmunization. Only RZV recipients maintained higher postvaccination gE-specific IL-2+ and IFN-γ+ and VZV-specific IL-2+ responses for 5 years. The 5-year persistence of VZV-specific memory and gE-specific Th1 immunity may underlie superior RZV efficacy. Clinical Trials Registration NCT02114333. [ABSTRACT FROM AUTHOR]

Giovanni Gabutti,1 Niccolò Bolognesi,2 Federica Sandri,2 Caterina Florescu,2 Armando Stefanati11Department of Medical Sciences, University of Ferrara, Ferrara, Italy; 2Postgraduate School of Hygiene and Preventive Medicine, University of Ferrara, Ferrara, ItalyAbstract: Varicella zoster virus (VZV) is the etiological agent of varicella, a highly infectious, self-limiting disease with serious complications. The decline in cell-mediated immunity (CMI) that occurs with aging or immunodepression causes a reactivation of the latent VZV as herpes zoster (HZ). Prevention of VZV through varicella vaccination strategies allows to avoid the primary infection in newborns and susceptible subjects. Available monovalent and combined VZV vaccines are effective, safe and generally well tolerated. Universal varicella vaccination has significantly impacted on incidence, complications and deaths related to this disease. Prevention of HZ through vaccination is a priority to avoid the significant burden of its incidence and complications. Currently two HZ vaccines are available. The recombinant zoster vaccine (RZV), approved by the FDA in 2017 and Zoster Vaccine Live (ZVL) licensed in the United States by the FDA in 2006. The advisory committee on immunization practices (ACIP) preferentially recommends RZV. ZVL remains an option for prevention of HZ in immunocompetent adults aged ≥60 years, although the CMI tends to wane a few years after vaccination.Keywords: epidemiology, varicella vaccine, recombinant zoster vaccine, Zoster Vaccine Live, vaccination strategies

There are two licensed herpes zoster vaccines. One is a live vaccine (ZVL) based on an attenuated varicella-zoster virus (VZV). The other is a recombinant vaccine (RZV) based on the VZV glycoprotein E (gE) combined with AS01B, a multicomponent adjuvant system. RZV is superior to ZVL in efficacy, and differs from ZVL in that protection is not diminished by the age of the vaccinee and has not waned significantly during 4 years of follow-up. Immunologic studies demonstrated higher peak memory and persistence of T cell responses in RZV compared with ZVL recipients. RZV recipients also showed development and persistence of polyfunctional T cell responses. Taken together, we conclude that the immunologic data parallel and support the higher efficacy over time of RZV compared with ZVL.

The recombinant zoster vaccine (Shingrix) was approved to help combat the incidence of shingles in patients age 50 years and older and the CDC now recommends it over the zoster vaccine live (Zostavax). This article highlights practical considerations to help clinicians appropriately apply the most recent vaccine recommendations to their patients. [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]

Protection against zoster conferred by zoster vaccine live (ZVL; Zostavax) wanes over time. We compared varicella-zoster virus cell-mediated immunity (VZV-CMI) of adults ≥70 years who received a second dose of ZVL ≥10 years after the initial dose with de novo-immunized age-matched controls. Before and during the first year after vaccination, VZV-CMI was significantly higher in reimmunized compared with de novo vaccinees. At 3 years, VZV-CMI differences between groups decreased and only memory responses remained marginally higher in reimmunized participants. In conclusion, the increase in VZV-CMI generated by reimmunization with ZVL is at least equally persistent compared with de novo immunization. [ABSTRACT FROM AUTHOR]

Abstract Background Herpes zoster (shingles) is a common viral disease increasing in risk and severity with age. Post-herpetic neuralgia (PHN), a complication of shingles, causes severe pain impacting quality of life (QoL). Zoster Vaccine Live (ZVL), a licensed vaccine for the prevention of shingles in the United Kingdom (UK), is part of the national immunisation programme (NIP) for adults aged 70–79. Public Health England (PHE) reports show shingles vaccine coverage varies, but is typically 50–60% across eligible cohorts. Materials/methods This retrospective, matched cohort study was conducted using The Health Improvement Network (THIN) UK primary care database. Individuals aged 70–79 were classified based on their vaccination status between September 2013 and May 2016. Risk and incidence rates for shingles were calculated for both groups over the duration of the study (mean 1.2 years). Vaccine effectiveness (VE) was calculated using the equation 1-relative risk (RR) for shingles and PHN. Results Within the total cohort (n = 295,135), 70,867 (24%) were vaccinated and 224,268 (76%) were unvaccinated. 2435 (0.83%) patients developed shingles: 241 (0.34%) among the vaccinated and 2194 (0.98%) among the unvaccinated. The VE for preventing shingles was 65.3% (95% CI: 60.3–69.6%). The incidence rate in the vaccinated group was 2.95 (95% CI: 2.59–3.34) vs 8.02 (95% CI: 7.68–8.36) per 1000 person years in the unvaccinated group. Risk of PHN was 0.02% and 0.06% in the respective vaccinated and unvaccinated groups. The VE for preventing PHN was 72% (95% CI: 50.0–83.9%). PHN incidence rates were 0.16 (95% CI: 0.08–0.27) and 0.53 (95% CI: 0.44–0.62) per 1000 person years in the vaccinated and unvaccinated groups, respectively. Conclusions ZVL reduced the risk of shingles among an elderly population. Given the negative impact of shingles and PHN on QoL, the benefits of vaccination are clear. Improving uptake in the UK is needed in this population. [ABSTRACT FROM AUTHOR]

Purpose. Published literature on the efficacy and safety of the herpes zoster (HZ) subunit vaccine (HZ/su vaccine) in reducing the risks of HZ and postherpetic neuralgia (PHN) in adults 50 years of age and older, as well as the vaccine's properties and efficacy relative to live attenuated vaccine, is reviewed. Summary. HZ/su vaccine (Shingrix, GlaxoSmithKline) is a recently Food and Drug Administration (FDA)--approved vaccine indicated for the prevention of HZ in adults 50 years of age and older. Based on several Phase III trials, the Advisory Committee on Immunization Practices has preferentially recommended HZ/su vaccine over a live attenuated vaccine previously approved by FDA. Reported overall HZ/su vaccine efficacy in preventing HZ in Phase III trials ranged from 89.8% to 97.2%. Compared with placebo use, HZ/su vaccine in those trials was associated with higher rates of transient local and systemic adverse events (AEs) but similar rates of serious vaccine-related AEs. Other clinical trials of HZ/su vaccine have yielded favorable results in various populations, including adults with a history of HZ, older adults who previously received live attenuated zoster vaccine, adults with human immunodeficiency virus infection, and stem cell transplant recipients. Conclusion. HZ/su vaccine is a recently approved, preferred option to reduce the risks of HZ and PHN in adults 50 years of age or older. Pain at the injection site is the most common AE associated with use of the vaccine. [ABSTRACT FROM AUTHOR]

We studied the relationship between varicella-zoster virus (VZV) DNAemia and development of VZV-specific immunity after administration of live-attenuated zoster vaccine. VZV-DNAemia, detected by polymerase chain reaction (PCR), and VZV-specific effector (Teff) and memory (Tmem) T cells, was measured in 67 vaccinees. PCR was positive in 56% (9 direct, 28 nested) on day 1 and in 16% (1 direct, 10 nested) on day 14. Teff progressively increased in direct-PCR-positive vaccinees up to day 30, but Tmem did not. Conversely, Tmem, but not Teff, increased in direct-PCR-negative vaccinees on day 7. The kinetics of these immune responses and VZV DNAemia suggested that direct-PCR sample positive represented viremia. [ABSTRACT FROM AUTHOR]

Background Zoster vaccine is a single dose live, attenuated vaccine (ZVL) indicated for individuals ≥50 years-old for the prevention of herpes zoster (HZ). Safety data from clinical trials and post-licensure studies provided reassurance that ZVL is generally safe and well tolerated. The objective of this review was to provide worldwide post-marketing safety information following 10 years of use and >34 million doses distributed. Methods All post-marketing adverse experience (AE) reports received worldwide between 02-May-2006 and 01-May-2016 from healthcare professionals following vaccination with ZVL and submitted to the MSD AE global safety database, were analyzed. Results A total of 23,556 AE reports, 93% non-serious, were reported. Local injection site reactions (ISRs), with a median time-to-onset of 2 days, were the most frequently reported AEs followed by HZ. The majority of HZ reports were reported within 2 weeks of vaccination and considered, based on time-to-onset, pathogenesis of HZ, and data from clinical trials, to be caused by wild-type varicella-zoster virus (VZV). HZ confirmed by PCR analysis to be VZV Oka/Merck vaccine-strain was identified in an immunocompetent individual 8 months postvaccination and in 4 immunocompromised individuals. Disseminated HZ was reported very rarely (<1%) with 38% occurring in immunocompromised individuals. All reports of disseminated HZ confirmed by PCR as VZV Oka/Merck vaccine-strain were in individuals with immunosuppressive conditions and/or therapy at the time of vaccination. Conclusions The safety profile of ZVL, following 10 years of post-marketing use, was favorable and consistent with that observed in clinical trials and post-licensure studies. [ABSTRACT FROM AUTHOR]

Background: Herpes zoster (HZ) and associated complications cause significant burden to older people. A HZ vaccination programme was introduced in Aotearoa New Zealand in April 2018 with a single dose vaccine for those aged 65 years and a four-year catch up for 66-80 year-olds. This study aimed to assess the 'real-world' effectiveness of the zoster vaccine live (ZVL) against HZ and postherpetic neuralgia (PHN)., Methods: We conducted a nationwide retrospective matched cohort study from 1 April 2018 to 1 April 2021 using a linked de-identified patient level Ministry of Health data platform. A Cox proportional hazards model was used to estimate ZVL vaccine effectiveness (VE) against HZ and PHN adjusting for covariates. Multiple outcomes were assessed in the primary (hospitalised HZ and PHN - primary diagnosis) and secondary (hospitalised HZ and PHN: primary and secondary diagnosis, community HZ) analyses. A sub-group analysis was carried out in, adults ≥ 65 years old, immunocompromised adults, Māori, and Pacific populations., Findings: A total of 824,142 (274,272 vaccinated with ZVL matched with 549,870 unvaccinated) New Zealand residents were included in the study. The matched population was 93.4% immunocompetent, 52.2% female, 80.2% European (level 1 ethnic codes), and 64.5% were 65-74 years old (mean age = 71.1±5.0). Vaccinated versus unvaccinated incidence of hospitalised HZ was 0.16 vs. 0.31/1,000 person-years and 0.03 vs. 0.08/1000 person-years for PHN. In the primary analysis, the adjusted overall VE against hospitalised HZ and hospitalised PHN was 57.8% (95% CI: 41.1-69.8) and 73.7% (95% CI:14.0-92.0) respectively. In adults ≥ 65 years old, the VE against hospitalised HZ was 54.4% (95% CI: 36.0-67.5) and VE against hospitalised PHN was 75·5% (95% CI: 19.9-92.5). In the secondary analysis, the VE against community HZ was 30.0% (95% CI: 25.6-34.5). The ZVL VE against hospitalised HZ for immunocompromised adults was 51.1% (95% CI: 23.1-69.5), and PHN hospitalisation was 67.6% (95% CI: 9.3-88.4). The VE against HZ hospitalisation for Māori was 45.2% (95% CI: -23.2-75.6) and for Pacific Peoples was 52.2% (95% CI: -40.6 -83·7)., Interpretation: ZVL was associated with a reduction in risk of hospitalisation from HZ and PHN in the New Zealand population., Funding: Wellington Doctoral Scholarship awarded to JFM., Competing Interests: Professor Simpson reports grants from the UK National Institute for Health Research, UK Medical Research Council, the NZ Health Research Council and Ministry of Business Innovation and Employment. Dr. Nguyen reports grants from the NZ Ministry of Business Innovation and Employment. Dr Janine Paynter reports grants (2021) and consulting fees (2019) from GlaxoSmithKline (all grants and consulting fees were institutional), the NZ Health Research Council, the NZ Ministry of Health, and a travel grant from GAVI, The Vaccine Alliance. All other authors declare no competing interests., (© 2022 The Authors.)