Immune response to the recombinant herpes zoster vaccine in people living with HIV over 50 years of age compared to non-HIV age-/gender-matched controls (SHINGR'HIV): a multicenter, international, non-randomized clinical trial study protocol.

BACKGROUND: The burden of herpes zoster (shingles) virus and associated complications, such as post-herpetic neuralgia, is higher in older adults and has a significant impact on quality of life. The incidence of herpes zoster and post-herpetic neuralgia is increased in people living with HIV (PLWH) compared to an age-matched general population, including PLWH on long-term antiretroviral therapy (ART) with no detectable viremia and normal CD4 counts. PLWH - even on effective ART may- exhibit sustained immune dysfunction, as well as defects in cells involved in the response to vaccines. In the context of herpes zoster, it is therefore important to assess the immune response to varicella zoster virus vaccination in older PLWH and to determine whether it significantly differs to that of HIV-uninfected healthy adults or younger PLWH. We aim at bridging these knowledge gaps by conducting a multicentric, international, non-randomised clinical study (SHINGR'HIV) with prospective data collection after vaccination with an adjuvant recombinant zoster vaccine (RZV) in two distinct populations: in PLWH on long-term ART (> 10 years) over 50 years of and age/gender matched controls. METHODS: We will recruit participants from two large established HIV cohorts in Switzerland and in France in addition to age-/gender-matched HIV-uninfected controls. Participants will receive two doses of RZV two months apart. In depth-evaluation of the humoral, cellular, and innate immune responses and safety profile of the RZV will be performed to address the combined effect of aging and potential immune deficiencies due to chronic HIV infection. The primary study outcome will compare the geometric mean titer (GMT) of gE-specific total IgG measured 1 month after the second dose of RZV between different age groups of PLWH and between PLWH and age-/gender-matched HIV-uninfected controls. DISCUSSION: The SHINGR'HIV trial will provide robust data on the immunogenicity and safety profile of RZV in older PLWH to support vaccination guidelines in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05575830. Registered on 12 October 2022. Eu Clinical Trial Register (EUCT number 2023-504482-23-00).

Herpes Virus Infections in Kidney Transplant Patients (HINT) - a prospective observational cohort study.

BACKGROUND: Kidney transplant recipients receive maintenance immunosuppressive therapy to avoid allograft rejection resulting in increased risk of infections and infection-related morbidity and mortality. Approximately 98% of adults are infected with varicella zoster virus, which upon reactivation causes herpes zoster. The incidence of herpes zoster is higher in kidney transplant recipients than in immunocompetent individuals, and kidney transplant recipients are at increased risk of severe herpes zoster-associated disease. Vaccination with adjuvanted recombinant glycoprotein E subunit herpes zoster vaccine (RZV) prevents herpes zoster in older adults with excellent efficacy (90%), and vaccination of kidney transplant candidates is recommended in Danish and international guidelines. However, the robustness and duration of immune responses after RZV vaccination, as well as the optimal timing of vaccination in relation to transplantation remain unanswered questions. Thus, the aim of this study is to characterize the immune response to RZV vaccination in kidney transplant candidates and recipients at different timepoints before and after transplantation. METHODS: The Herpes Virus Infections in Kidney Transplant Patients (HINT) study is a prospective observational cohort study. The study will include kidney transplant candidates on the waiting list for transplantation (n = 375) and kidney transplant recipients transplanted since January 1, 2019 (n = 500) from all Danish kidney transplant centers who are offered a RZV vaccine as routine care. Participants are followed with repeated blood sampling until 12 months after inclusion. In the case of transplantation or herpes zoster disease, additional blood samples will be collected until 12 months after transplantation. The immune response will be characterized by immunophenotyping and functional characterization of varicella zoster virus-specific T cells, by detection of anti-glycoprotein E antibodies, and by measuring cytokine profiles. DISCUSSION: The study will provide new knowledge on the immune response to RZV vaccination in kidney transplant candidates and recipients and the robustness and duration of the response, potentially enhancing preventive strategies against herpes zoster in a population at increased risk. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05604911).

Skin manifestations after immunisation with an adjuvanted recombinant zoster vaccine, Germany, 2020.

BackgroundShortly after the launch of a novel adjuvanted recombinant zoster vaccine (RZV), Shingrix, cases of suspected herpes zoster (HZ) or zoster-like skin reactions following immunisation were reported.AimWe aimed to investigate if these skin manifestations after administration of RZV could be HZ.MethodsBetween April and October 2020, general practitioners (GP) reporting a suspected case of HZ or zoster-like skin manifestation after RZV vaccination to the Paul-Ehrlich-Institut, the German national competent authority, were invited to participate in the study. The GP took a sample of the skin manifestation, photographed it and collected patient information on RZV vaccination and the suspected adverse event. We analysed all samples by PCR for varicella-zoster virus (VZV) and herpes-simplex virus (HSV) and genotyped VZV-positive samples. In addition, cases were independently assessed by two dermatologists.ResultsEighty eligible cases were enrolled and 72 could be included in the analysis. Of the 72 cases, 45 were female, 33 were 60-69 years old, 32 had skin symptoms in the thoracic and 27 in the cervical dermatomes. Twenty-seven samples tested PCR positive for VZV (all genotyped as wild-type, WT), three for HSV-1 and five for HSV-2.ConclusionIt may be difficult to distinguish HZ, without a PCR result, from other zoster-like manifestations. In this study, VZV-PCR positive dermatomal eruptions occurring in the first weeks after immunisation with RZV were due to WT VZV, which is not unexpected as HZ is a common disease against which the vaccine is unlikely to provide full protection at this time.

Prevention of Shingles in Dermatology Patients on Systemic Medications.

The lifetime risk for herpes zoster (HZ) of approximately 1 in 3 is increased with advancing age, a family history of HZ, diseases with altered immune function, immunosuppression, physical trauma and psychological stress. In dermatology, monotherapy with current biologics does not increase risk, however systemic steroids, Janus kinase inhibitors and combination biologic/conventional disease-modifying antirheumatics do. The recombinant zoster vaccine (RZV, Shingrix®), an adjuvanted non-live subunit vaccine against the glycoprotein E subunit of varicella zoster virus, is approved for prevention of HZ in adults ≥50 years of age, and adults ≥18 years of age who are or will be at increased risk of HZ due to immunodeficiency or immunosuppression due to disease or treatment. It is administered as two 0.5 ml intramuscular injections 2-6 months apart. In immunocompromised individuals, the spacing between injections may be reduced to 1-2 months. Where possible, the first dose should be administered at least 14 days before onset of immunosuppressive treatment. Studies in immunocompetent individuals have shown high efficacy including prevention of HZ, postherpetic neuralgia and other complications, with persistence of effect 10 years after vaccination. The acceptable safety profile and efficacy in five different immunocompromised populations support its use in at-risk adult dermatologic patients.

Herpes Zoster and Vaccination Strategies in Inflammatory Bowel Diseases: A Practical Guide.

Herpes zoster is a painful dermatomal cutaneous eruption resulting from reactivation of the latent varicella-zoster virus. Patients with inflammatory bowel diseases have an increased risk of shingles compared with the general population and this risk can be increased with the use of immunosuppressive therapy. Live zoster vaccine and recombinant zoster vaccine have shown efficacy for the prevention of herpes zoster. The recombinant zoster vaccine seems to offer greater efficacy and long-term protection profile compared with the life zoster vaccine. However, their use in clinical practice still is unclear and updated vaccination recommendations are lacking. This review discusses the risk for shingles in patients with inflammatory bowel diseases, available vaccines, and their efficacy and safety profiles. We also provide guidance on who, when, and how to vaccinate for herpes zoster in routine clinical practice among patients with inflammatory bowel diseases.

Efficacy of Recombinant Zoster Vaccine in Patients With Inflammatory Bowel Disease.

BACKGROUND & AIMS: Individuals with inflammatory bowel disease (IBD) have an increased risk of herpes zoster (HZ) infection. Although the efficacy of recombinant zoster vaccine (RZV) is high among immunocompetent individuals, little is known about its effect among immunosuppressed individuals with IBD. METHODS: We conducted a retrospective cohort study among individuals in the national Veterans Affairs Healthcare System diagnosed with IBD on or before January 3, 2018, the earliest date of RZV vaccinations. We collected data on 7008 and 26,292 eligible patients with IBD in the 50- to 60-year and >60-year age groups, respectively. We identified veterans who received RZV and compared the incidence of HZ between vaccinated versus unvaccinated individuals. We performed multivariable Cox regression with time varying analysis to determine the risk of HZ among the vaccinated (full dose and single dose separately) versus unvaccinated cohort, stratified by IBD medications. RESULTS: The crude HZ incidence rate after full dose vaccination of RZV when compared with the unvaccinated group was lower in both the 50- to 60-year age group (0.00 vs 3.93 per 1000 person-years) and >60-year age group (1.80 vs 4.57 per 1000 person-years). RZV vaccination was associated with a significantly lower risk of HZ among the 50- to 60-year and >60-year age groups, although this was limited by low HZ event rates. CONCLUSION: RZV vaccination was associated with decreased risk of HZ infection among both the 50- to 60-year and >60-year age groups. Greater efforts should be made to vaccinate all patients with IBD with RZV.

Recombinant Zoster Vaccine (Shingrix): Real-World Effectiveness in the First 2 Years Post-Licensure.

BACKGROUND: Shingrix (recombinant zoster vaccine) was licensed to prevent herpes zoster, dispensed as 2 doses given 2-6 months apart among adults aged ≥50 years. Clinical trials yielded efficacy of >90% for confirmed herpes zoster, but post-market performance has not been evaluated. Efficacy of a single dose and a delayed second dose and efficacy among persons with autoimmune or immunosuppressive conditions have not been studied. We aimed to assess post-market vaccine effectiveness of Shingrix. METHODS: We conducted a cohort study among Medicare Part D community-dwelling beneficiaries aged >65 years. Herpes zoster was identified using a medical office visit diagnosis with treatment, and postherpetic neuralgia was identified using a validated algorithm. We used inverse probability of treatment weighting to improve cohort balance and marginal structural models to estimate hazard ratios. RESULTS: We found a vaccine effectiveness of 70.1% (95% confidence interval [CI], 68.6-71.5) and 56.9% (95% CI, 55.0-58.8) for 2 and 1 doses, respectively. The 2-dose vaccine effectiveness was not significantly lower for beneficiaries aged >80 years, for second doses received at ≥180 days, or for individuals with autoimmune conditions. The vaccine was also effective among individuals with immunosuppressive conditions. Two-dose vaccine effectiveness against postherpetic neuralgia was 76.0% (95% CI, 68.4-81.8). CONCLUSIONS: This large real-world observational study of the effectiveness of Shingrix demonstrates the benefit of completing the 2-dose regimen. Second doses administered beyond the recommended 6 months did not impair effectiveness. Our effectiveness estimates were lower than the clinical trials estimates, likely due to differences in outcome specificity.

Effectiveness of the Recombinant Zoster Vaccine in Adults Aged 50 and Older in the United States: A Claims-Based Cohort Study.

BACKGROUND: The recombinant zoster vaccine had over 90% efficacy in preventing herpes zoster in clinical trials. However, its effectiveness outside of a clinical trial setting has not been investigated. This study aimed to assess the effectiveness of the recombinant zoster vaccine in general practice. METHODS: A de-identified administrative claims database, the OptumLabs Data Warehouse, was used to conduct this retrospective cohort study to assess the effectiveness of the recombinant zoster vaccine against herpes zoster in nonimmunocompromised, vaccine age-eligible individuals enrolled in the database for ≥365 days. RESULTS: A total of 4 769 819 adults were included in this study, with 173 745 (3.6%) adults receiving 2 valid doses of the recombinant zoster vaccine. The incidence rate of herpes zoster was 258.8 (95% confidence interval [CI], 230.0-289.4) cases per 100 000 person-years in vaccinated persons compared with 893.1 (95% CI, 886.2-900.0) in unvaccinated persons. Recombinant zoster vaccine effectiveness was 85.5% (95% CI, 83.5-87.3%) overall, with an effectiveness of 86.8% (95% CI, 84.6-88.7%) in individuals 50 to 79 years old compared with 80.3% (95% CI, 75.1-84.3%) in individuals aged 80 and older. In patients with a history of live zoster vaccine within 5 years of study inclusion, vaccine effectiveness was 84.8% (95% CI, 75.3-90.7%). CONCLUSIONS: Recombinant zoster vaccine effectiveness against herpes zoster was high in a real-world setting. Given the low vaccine coverage and high effectiveness, a major public health effort is needed to identify and address barriers to vaccination and increase immunization rates.

Identification and Characterization of CD4+ T Cell Epitopes after Shingrix Vaccination.

Infections with varicella-zoster virus (VZV) are associated with a range of clinical manifestations. Primary infection with VZV causes chicken pox. The virus remains latent in neurons, and it can reactivate later in life, causing herpes zoster (HZ). Two different vaccines have been developed to prevent HZ; one is based on a live attenuated VZV strain (Zostavax), and the other is based on adjuvanted gE recombinant protein (Shingrix). While Zostavax efficacy wanes with age, Shingrix protection retains its efficacy in elderly subjects (individuals 80 years of age and older). In this context, it is of much interest to understand if there is a role for T cell immunity in the differential clinical outcome and if there is a correlate of protection between T cell immunity and Shingrix efficacy. In this study, we characterized the Shingrix-specific ex vivo CD4 T cell responses in the context of natural exposure and HZ vaccination using pools of predicted epitopes. We show that T cell reactivity following natural infection and Zostavax vaccination dominantly targets nonstructural (NS) proteins, while Shingrix vaccination redirects dominant reactivity to target gE. We mapped the gE-specific responses following Shingrix vaccination to 89 different gE epitopes, 34 of which accounted for 80% of the response. Using antigen presentation assays and single HLA molecule-transfected lines, we experimentally determined HLA restrictions for 94 different donor/peptide combinations. Finally, we used our results as a training set to assess strategies to predict restrictions based on measured or predicted HLA binding and the corresponding HLA types of the responding subjects.IMPORTANCE Understanding the T cell profile associated with the protection observed in elderly vaccinees following Shingrix vaccination is relevant to the general definition of correlates of vaccine efficacy. Our study enables these future studies by clarifying the patterns of immunodominance associated with Shingrix vaccination, as opposed to natural infection or Zostavax vaccination. Identification of epitopes recognized by Shingrix-induced CD4 T cells and their associated HLA restrictions enables the generation of tetrameric staining reagents and, more broadly, the capability to characterize the specificity, magnitude, and phenotype of VZV-specific T cells.

Safety of recombinant zoster vaccine: a retrospective study of 622 rheumatology patients.

OBJECTIVES: To provide insight into the safety of recombinant zoster vaccine (RZV) in patients with immune-mediated inflammatory diseases (IMID). METHODS: Patients who received RZV in a single-centre rheumatology department were retrospectively included. An IMID flare was defined as (i) a documentation of flare in the office notes or patient portal communication or (ii) new prednisone prescription, in the 12 weeks after each dose. RESULTS: Six-hundred and twenty-two patients were included (67% female, median age 67 years), 8.5% of them experienced adverse events (AEs) and herpes zoster (HZ) incidence was 0.6% after median follow-up of 36 weeks. Of 359 IMID patients: 88 had RA (25%), 50 vasculitis (14%) and 29 PMR (8%). At vaccination, 35% were on glucocorticoids (GC). Fifty-nine patients (16%) experienced a flare, 18 flares occurred in temporal relation to a treatment change (31%). RA patients had the highest flare rate (n = 21, 24%), 25% of patients who flared required adjustment of immunosuppression. In a multivariate analysis, use of GC at time of vaccination was associated with flare after vaccination [odds ratio (OR) 2.31 (1.3-4.1), P =0.004]. A time-to-flare survival analysis (Cox-model) showed that GC was a significant predictor of IMID flare after first RZV dose [hazard ratio (HR) 2.4 (1.3-4.5), P =0.0039] and that a flare after the first dose was associated with flaring after the second RZV dose [HR 3.9 (1.7-9), P =0.0015]. CONCLUSION: RZV administration in patients with IMIDs was generally well-tolerated, though mild flares were not uncommon in the first 12 weeks after vaccination. These data may provide useful information for patient education when considering RZV administration.

Effectiveness of the Recombinant Zoster Vaccine for Herpes Zoster Ophthalmicus in the United States.

PURPOSE: To examine the effectiveness of the recombinant zoster vaccine (RZV) for preventing herpes zoster ophthalmicus (HZO) in the general United States population. DESIGN: Retrospective, observational cohort study. PARTICIPANTS: Individuals enrolled in the OptumLabs Data Warehouse (OLDW; OptumLabs, Cambridge, MA) who were age eligible for herpes zoster (HZ) vaccination (≥50 years of age) from 2018 through 2019. The OLDW is a longitudinal, de-identified administrative claims and electronic health record database of patients in the United States with commercial insurance, Medicare Part D, or Medicare Advantage METHODS: Patients were required to have 365 days or more of continuous enrollment to be eligible. Those with a diagnosis code of HZ or an immunocompromising condition within 1 year before study inclusion were excluded. Vaccination with the RZV was ascertained by Current Procedural Terminology codes, and HZO was ascertained by International Classification of Diseases, Tenth Revision, codes. Cox proportional hazards regression models were used to estimate the hazard ratio of HZO associated with RZV, and inverse-probability weighting was used to control for confounding. Vaccine effectiveness was calculated from hazard ratios. MAIN OUTCOME MEASURES: Incidence of HZO in vaccinated versus unvaccinated person-times and vaccine effectiveness were assessed. RESULTS: From January 1, 2018, through December 31, 2019, a total of 4 842 579 individuals were included in this study. One hundred seventy-seven thousand two hundred eighty-nine (3.7%) received 2 valid doses of RZV. The incidence rate of HZO was 25.5 cases (95% confidence interval [CI], 17.4-35.8 cases) per 100 000 person-years in the vaccinated group compared with 76.7 cases (95% CI, 74.7-78.7 cases) in the unvaccinated group. The overall adjusted effectiveness of RZV against HZO was 89.1% (95% CI, 82.9%-93.0%). CONCLUSIONS: The effectiveness of RZV against HZO in individuals 50 years of age and older is high in a clinical setting. However, the low vaccination rate in this study highlights the public health need to increase HZV use. Ophthalmologists can play an important role in recommending vaccination to eligible patients.

A systematic review of herpes zoster incidence and consensus recommendations on vaccination in adult patients on systemic therapy for psoriasis or psoriatic arthritis: From the Medical Board of the National Psoriasis Foundation.

BACKGROUND: Herpes zoster (HZ) incidence is linked to immunosuppression. Patients with psoriasis or psoriatic arthritis (PsA) on systemic therapy might be at an increased risk for HZ. OBJECTIVE: To assess HZ risk in patients with psoriasis and PsA by systemic treatment and provide recommendations regarding HZ vaccination. METHODS: A systematic literature search was performed for HZ in patients with psoriasis and PsA. HZ vaccination guidelines were reviewed, and the medical board of the National Psoriasis Foundation made consensus recommendations in psoriasis and PsA patients using graded evidence. RESULTS: In total, 41 studies met inclusion criteria. Systemic corticosteroids (strong, 1), tofacitinib (strong, 1), and combination therapy with biologic and conventional synthetic disease-modifying antirheumatic drugs (weak, 2a) carry increased HZ risk while monotherapy does not. There is insufficient evidence to determine risk with interleukin 12/23, 17, and 23 inhibitors or apremilast (weak, 2a). Recombinant zoster vaccine is recommended for all psoriasis and PsA patients >50 years old and patients <50 years old on tofacitinib, systemic steroids, or combination systemic treatment. Vaccination of patients <50 years old on other systemic therapies may be considered on a case-by-case basis. LIMITATIONS: There was significant heterogeneity between studies. CONCLUSION: HZ risk depends on disease severity and treatment class. Recombinant zoster vaccine should be given to all psoriasis and PsA patients >50 years old and younger patients at increased risk.

Shingrix for Herpes Zoster: A Review

Herpes zoster (HZ), also known as shingles, results from reactivation of the latent varicella-zoster virus (VZV), which commonly causes chickenpox in childhood. Greater than 90% of adults are infected with this virus, putting them at risk for reactivation. HZ presents as a painful, vesicular rash distributed in a unilateral and dermatomal pattern along dorsal root or cranial nerve ganglia. The rash often presents with prodromal symptoms and progresses to include clear vesicular clusters, evolving through stages of pustulation, ulceration, and crusting. HZ therapy currently involves the use of antiviral agents and pain management; however, HZ prophylaxis has been strongly recommended in older adults through vaccination with a live attenuated vaccine, Zostavax®. A new recombinant subunit vaccine, HZ/su (Shingrix®), is the subject of this review. In clinical trials, HZ/su demonstrated an overall vaccine efficacy of 97.2% among participants 50 years of age or older, indicating a significantly reduced risk of HZ in these individuals. Shingrix® was approved by the US FDA in October 2017 as HZ prophylaxis.

Post-marketing surveillance of 10,392 herpes zoster vaccines doses in Australia.

BACKGROUND: Immunisation against herpes zoster is recommended for adults aged ≥ 50 years. Two vaccines, a live attenuated (ZVL, Zostavax®) and an adjuvant recombinant subunit (HZ/su, Shingrix®), are available in Australia. Immunisation guidelines are shifting their recommendations towards HZ/su because of higher efficacy in preventing herpes zoster and associated complications. However, there are limited post-marketing data comparing the safety profiles of these vaccines. METHODS: Data from SmartVax, an active surveillance system for monitoring adverse events following immunisation (AEFIs) utilised by > 450 clinics throughout Australia, were analysed. Data from patients aged ≥ 50 years, who received ZVL or HZ/su, from 1 June 2021 to 31 May 2022, at clinics that utilised SmartVax were included. The proportion of records where patients who reported any, local, and systemic AEFIs after receiving ZVL or HZ/su were compared using multivariable logistic regression models. RESULTS: Data from 10,392 immunisation records (n = 8341 ZVL; n = 2051 HZ/su) were included. The proportion of AEFIs reported was higher with HZ/su (41.9 % [any], 33.8 % [local], 25.2 % [systemic]) than with ZVL (8.7 % [any], 6.2 % [local], 3.5 % [systemic]). After controlling for demographic variables, HZ/su presented a 6-fold increase in the odds (OR 6.44; 95 %CI: 5.57-7.46) of a reported AEFI compared to ZVL. Only 59 (0.6 %) of vaccinations lead to medical attention being sought due to an AEFI. CONCLUSIONS: While rates of AEFIs was higher with HZ/su than ZVL, most AEFIs were mild and did not require medical attention. Our findings support the change in vaccine recommendations and the use of HZ/su in immunisation programs.

Anti-Herpes Zoster Vaccination of Fragile Patients in Hospital Setting: A Nudge Intervention in Italy.

BACKGROUND: A nudge intervention against Herpes Zoster, created and implemented in Italy, is presented in order to administer the Shingrix vaccine on a sample of frail patients, as required by the National Prevention Plan. Individual and contextual factors associated with vaccine adherence were investigated. METHOD: 300 frail adult subjects underwent a full vaccine cycle with recombinant-Shingrix vaccine (RZV vaccine). Hospital Presidia of the Salerno University Hospital Authority, a Hospital Presidium of the Salerno Local Health Authority, and the Public Health Laboratory of the University of Salerno (Campania) participated in the intervention. An ad hoc questionnaire was administered with the following scales: EQ-5D, PSS-10, MSPSS, and representations of HZ and its consequences. RESULTS: Some variables, such as peer support, doctor-patient relationship, level of education, and perception of health, are important in vaccine adherence and information processing. The following factors emerged from the factor analysis: Trust in collective knowledge and collective responsibility (F1); beliefs about virus risk and vaccine function (F2); information about virus and symptomatology (F3); and vaccine distrust (F4). Factor 4 correlates negatively with social support indices (R = -0.363; p < 0.001). There is a significant relationship between factor 3 and satisfaction with national information campaigns (F = 3.376; gdl = 5; p-value = 0.006). CONCLUSIONS: Future vaccination campaigns should be built with the aim of personalizing information and developing contextualized strategies, starting from understanding the stakeholders involved, cultural contexts, and organizational settings.

Herpes zoster mRNA vaccine induces superior vaccine immunity over licensed vaccine in mice and rhesus macaques.

Herpes zoster remains an important global health issue and mainly occurs in aged and immunocompromised individuals with an early exposure history to Varicella Zoster Virus (VZV). Although the licensed vaccine Shingrix has remarkably high efficacy, undesired reactogenicity and increasing global demand causing vaccine shortage urged the development of improved or novel VZV vaccines. In this study, we developed a novel VZV mRNA vaccine candidate (named as ZOSAL) containing sequence-optimized mRNAs encoding full-length glycoprotein E encapsulated in an ionizable lipid nanoparticle. In mice and rhesus macaques, ZOSAL demonstrated superior immunogenicity and safety in multiple aspects over Shingrix, especially in the induction of strong T-cell immunity. Transcriptomic analysis revealed that both ZOSAL and Shingrix could robustly activate innate immune compartments, especially Type-I IFN signalling and antigen processing/presentation. Multivariate correlation analysis further identified several early factors of innate compartments that can predict the magnitude of T-cell responses, which further increased our understanding of the mode of action of two different VZV vaccine modalities. Collectively, our data demonstrated the superiority of VZV mRNA vaccine over licensed subunit vaccine. The mRNA platform therefore holds prospects for further investigations in next-generation VZV vaccine development.

Reduction in Herpes Zoster Antiviral Use Since the Introduction of the Live-Attenuated Zoster Vaccine on Australia's National Immunisation Program: A Population-Based Study from 1994 to 2019.

INTRODUCTION: Zostavax, the live-attenuated vaccine used to prevent herpes zoster (HZ), has been available to individuals aged 70 and 71-79 years (phased catch-up) via Australia's National Immunisation Program (NIP) since 2016. There are limited data characterising the incidence of HZ at the level of the Australian population. National prescription data for antivirals used to treat HZ may be used as a proxy for HZ incidence. We aimed to examine trends in antiviral prescriptions supplied for the treatment of HZ in Australia pre- and post-2016, and to assess whether Zostavax's inclusion on the NIP correlated with a reduction in HZ antiviral prescription rates. METHODS: Using the Australian Pharmaceutical Benefits Scheme and Repatriation Pharmaceutical Benefits Scheme prescribing data, we analysed antiviral prescriptions supplied for the treatment of HZ Australia-wide between 1994 and 2019. Annual prescription rates were calculated, and trends and changes in HZ antiviral use were explored descriptively and using Poisson models. RESULTS: HZ antiviral prescription rates increased 2.6-fold (160%) between 1995 and 2015 [25.4 (95% CI 25.2, 25.6) and 65.3 (95% CI 64.9, 65.6) prescriptions per 10,000 people, respectively], and then decreased 0.45-fold (55%) between 2016 and 2018 [60.9 (95% CI 60.6, 61.2) and 27.5 (95% CI 27.3, 27.9) prescriptions per 10,000 people, respectively]. The prescription rate for the antiviral famciclovir restricted specifically for treating HZ in immunocompromised individuals increased 8.5-fold (750%) between 2006 (year first listed) and 2019 [0.3 (95% CI 0.3, 0.3) and 2.5 (95% CI 2.4, 2.6) prescriptions per 10,000 people, respectively]. CONCLUSION: The introduction of the live-attenuated HZ vaccine on Australia's formal national vaccination program was associated with a reduction in HZ antiviral prescription rates within the Australian population. The data suggest that the introduction of Shingrix, the non-live subunit zoster vaccine, may also be associated with a similar reduction in HZ antiviral prescriptions used to treat the immunocompromised, as well as the general population, given its accepted greater efficacy over Zostavax.

Reactivation of Herpes Zoster After Recombinant Vaccine (Shingrix): A Case Report.

Herpes zoster (HZ) is a common contagious dermatological condition that results from reactivation of varicella-zoster virus (VZV), which currently could be prevented by vaccination. We describe a rare case of varicella infection reactivation after routine zoster vaccination in an immunocompetent female in her 60s who developed dermatomal pruritic and vesicular rash one week after receiving Shingrix vaccine, along with fever, sweating, headache, and fatigue. The patient was treated as a case of herpes zoster reactivation with a seven days course of acyclovir. She continued to do well on follow-up with no significant complications. Though uncommon, it is important for healthcare providers to recognize this adverse reaction to expedite testing and treatment.

Status of Herpes Zoster and Herpes Zoster Vaccines in 2023: A position paper.

Herpes zoster infection (HZ) is an important public health problem due to its high incidence and frequent complications, especially post-herpetic neuropathy . The incidence of HZ increases with age and is more frequent in immunocompromised patients. It is estimated that at least 60,000 people develop HZ each year in Spain. The usual forms of HZ are so clinically characteristic that they do not usually require microbiological confirmation, which is reserved for cases without cutaneous manifestations or with atypical presentation. There are currently two vaccines approved by the regulatory agencies and marketed in Spain to prevent the onset of HZ and its complications. The first (Zostavax®) was marketed by the company MSD and licensed in Europe in 2006 and is a live attenuated virus vaccine that is administered in a single dose, while the second (Shingrix®) is a recombinant vaccine, marketed in 2017 and requires two doses. While the former cannot be administered to immunocompromised persons, the latter can be prescribed to any group of adults. The criteria for the indication and financing of these vaccines have not been uniform in the various autonomous communities of Spain. These and other aspects of HZ have been discussed by a group of experts from the Illustrious Official College of Physicians of Madrid (ICOMEM) whose criteria and opinions are included in this paper.