Metabolic Phenotypes of Response to Vaccination in Humans.

Herpes zoster (shingles) causes significant morbidity in immune compromised hosts and older adults. Whereas a vaccine is available for prevention of shingles, its efficacy declines with age. To help to understand the mechanisms driving vaccinal responses, we constructed a multiscale, multifactorial response network (MMRN) of immunity in healthy young and older adults immunized with the live attenuated shingles vaccine Zostavax. Vaccination induces robust antigen-specific antibody, plasmablasts, and CD4+ T cells yet limited CD8+ T cell and antiviral responses. The MMRN reveals striking associations between orthogonal datasets, such as transcriptomic and metabolomics signatures, cell populations, and cytokine levels, and identifies immune and metabolic correlates of vaccine immunity. Networks associated with inositol phosphate, glycerophospholipids, and sterol metabolism are tightly coupled with immunity. Critically, the sterol regulatory binding protein 1 and its targets are key integrators of antibody and T follicular cell responses. Our approach is broadly applicable to study human immunity and can help to identify predictors of efficacy as well as mechanisms controlling immunity to vaccination.

Varicella-zoster virus-related neurological complications: From infection to immunomodulatory therapies.

The Varicella-zoster virus (VZV), classified as a neurotropic member of the Herpesviridae family, exhibits a characteristic pathogenicity, predominantly inducing varicella, commonly known as chickenpox, during the initial infectious phase, and triggering the reactivation of herpes zoster, more commonly recognized as shingles, following its emergence from a latent state. The pathogenesis of VZV-associated neuroinflammation involves a complex interplay between viral replication within sensory ganglia and immune-mediated responses that contribute to tissue damage and dysfunction. Upon primary infection, VZV gains access to sensory ganglia, establishing latent infection within neurons. During reactivation, the virus can spread along sensory nerves, triggering a cascade of inflammatory mediators, chemokines, and immune cell infiltration in the affected neural tissues. The role of both adaptive and innate immune reactions, including the contributions of T and B cells, macrophages, and dendritic cells, in orchestrating the immune-mediated damage in the central nervous system is elucidated. Furthermore, the aberrant activation of the natural defence mechanism, characterised by the dysregulated production of immunomodulatory proteins and chemokines, has been implicated in the pathogenesis of VZV-induced neurological disorders, such as encephalitis, myelitis, and vasculopathy. The intricate balance between protective and detrimental immune responses in the context of VZV infection emphasises the necessity for an exhaustive comprehension of the immunopathogenic mechanisms propelling neuroinflammatory processes. Despite the availability of vaccines and antiviral therapies, VZV-related neurological complications remain a significant concern, particularly in immunocompromised individuals and the elderly. Elucidating these mechanisms might facilitate the emergence of innovative immunomodulatory strategies and targeted therapies aimed at mitigating VZV-induced neuroinflammatory damage and improving clinical outcomes. This comprehensive understanding enhances our grasp of viral pathogenesis and holds promise for pioneering therapeutic strategies designed to mitigate the neurological ramifications of VZV infections.

A comprehensive, updated systematic review and meta-analysis of epidemiologic evidence on the connection between herpes zoster infection and the risk of stroke.

Stroke is a common worldwide cause of death and disability, resulting from an obstruction or reduction in blood flow to the brain. Research has demonstrated that systemic infection such as herpes zoster (HZ) / ophthalmicus herpes zoster (HZO) can potentially trigger stroke. This study includes an updated systematic review and meta-analysis of the epidemiologic data on the connection between HZ/HZO infection and the risk of stroke. A meticulous search of different database yielded 905 studies. Furthermore, an additional 14 studies from a previous meta-analysis were incorporated. Eligible studies underwent rigorous screening, resulting in 18 papers. Statistical analyses, including random/fixed effects models and subgroup analyses, were conducted to assess pooled relative risk (RR) and heterogeneity. The meta-analysis consisted of 5,505,885 participants and found a statistically significant association between HZ infection and the risk of stroke (pooled RR = 1.22, 95% confidence interval [CI] 1.12-1.34). The HZO infection showed a significantly higher overall pooled RR of 1.71 (95% CI 1.06-2.75), indicating a strong connection with the risk of stroke. Subgroup analysis revealed that the odds ratio might play a significant role in causing heterogeneity. Time since infection emerged as a crucial factor, with heightened stroke risk in the initial year post-HZ/HZO exposure, followed by a decline after the first year. Asian/Non-Asian studies demonstrated varied results in HZ/HZO patients. Meta-analysis reveals a significant HZ/HZO-stroke link. Subgroups highlight varied risks and warrant extended Asian/non-Asian patient investigation.

Serious neurological adverse events in immunocompetent children and adolescents caused by viral reactivation in the years following varicella vaccination.

Serious adverse events following vaccination include medical complications that require hospitalisation. The live varicella vaccine that was approved by the Food and Drug Administration in the United States in 1995 has an excellent safety record. Since the vaccine is a live virus, adverse events are more common in immunocompromised children who are vaccinated inadvertently. This review includes only serious adverse events in children considered to be immunocompetent. The serious adverse event called varicella vaccine meningitis was first reported in a hospitalised immunocompetent child in 2008. When we carried out a literature search, we found 15 cases of immunocompetent children and adolescents with varicella vaccine meningitis; the median age was 11 years. Eight of the children had received two varicella vaccinations. Most of the children also had a concomitant herpes zoster rash, although three did not. The children lived in the United States, Greece, Germany, Switzerland, and Japan. During our literature search, we found five additional cases of serious neurological events in immunocompetent children; these included 4 cases of progressive herpes zoster and one case of acute retinitis. Pulses of enteral corticosteroids as well as a lack of herpes simplex virus antibody may be risk factors for reactivation in immunocompetent children. All 20 children with adverse events were treated with acyclovir and recovered; 19 were hospitalised and one child was managed as an outpatient. Even though the number of neurological adverse events remains exceedingly low following varicella vaccination, we recommend documentation of those caused by the vaccine virus.

Prior Herpes Simplex Virus Infection and the Risk of Herpes Zoster.

BACKGROUND: The incidence of herpes zoster (HZ) has increased in the United States concurrent with decrease in herpes simplex virus (HSV) prevalence. We hypothesized that lack of HSV-elicited cross-reactive immunity to varicella-zoster virus (VZV) results in an increased risk of HZ. Using specimens from the placebo arm of the Shingles Prevention Study, we investigated whether persons who develop HZ are less likely to have prior HSV infection than persons who do not develop HZ, and whether HZ is less severe in persons with HSV than in HSV seronegative persons. METHODS: We conducted a nested case-control (1:2) study comparing the seroprevalence of HSV-1 and HSV-2 in cases (persons with polymerase chain reaction-confirmed HZ) to age-, sex-, and health-matched controls (persons without HZ). RESULTS: Sera from 639 study participants (213 cases and 426 controls) yielded definitive HSV antibody results and were analyzed. Overall, HSV seropositivity rate was 75%. HSV seronegativity was significantly higher in HZ cases than controls (30.5% vs 22.3%; P = .024), with a 55% higher risk of HZ in HSV seronegative than HSV seropositive participants. HSV seropositivity was associated with more severe HZ (P = .021). CONCLUSIONS: Our study demonstrated that prior infection with HSV partly protects against HZ.

Unravelling the immune signature of herpes zoster: Insights into pathophysiology and the HLA risk profile.

The varicella-zoster virus (VZV) infects over 95% of the population. VZV reactivation causes herpes zoster (HZ), known as shingles, primarily affecting the elderly and immunocompromised individuals. However, HZ can also occur in otherwise healthy individuals. We analyzed the immune signature and risk profile in HZ patients using a genome-wide association study across different UK Biobank HZ cohorts. Additionally, we conducted one of the largest HZ HLA association studies to date, coupled with transcriptomic analysis of pathways underlying HZ susceptibility. Our findings highlight the significance of the MHC locus for HZ development, identifying five protective and four risk HLA alleles. This demonstrates that HZ susceptibility is largely governed by variations in the MHC. Furthermore, functional analyses revealed the upregulation of type I interferon and adaptive immune responses. These findings provide fresh molecular insights into the pathophysiology and the activation of innate and adaptive immune responses triggered by symptomatic VZV reactivation.

PROCESS Trial: Effect of Duloxetine Premedication for Postherpetic Neuralgia Within 72 Hours of Herpes Zoster Reactivation-A Randomized Controlled Trial.

BACKGROUND: Postherpetic neuralgia (PHN) is the most common chronic complication of herpes zoster (HZ) and results in severe refractory neuropathic pain. This study aimed at evaluating the efficacy of premedication with duloxetine in the prevention of PHN. METHODS: The PROCESS trial is a multicenter, randomized, open-label, blinded-endpoint trial used a 1:1 duloxetine:control ratio. Adults 50 years or older with HZ who presented with vesicles within 72 hours were recruited. The primary outcome was the incidence of PHN at 12 weeks. PHN was defined as any pain intensity score other than 0 mm on the visual analog scale (VAS) at week 12 after the onset of the rash. The secondary outcomes were the number of participants with VAS >0 and VAS ≥3. The modified intention-to-treat (mITT) principle and per-protocol (PP) principle were used for the primary outcome analysis. RESULTS: A total of 375 participants were randomly assigned to the duloxetine group and 375 were assigned to the control group. There was no significant difference in the incidence of PHN in the duloxetine group compared with the control group in the mITT analysis (86 [22.9%] of 375 vs 108 [28.8%] of 375; P = .067). PP analysis produced similar results. However, there were significant differences between the 2 groups in the number of participants with VAS >0 and VAS ≥3 (P < .05 for all comparisons). CONCLUSIONS: Although absolute prevention of PHN does not occur, this trial found that premedication with duloxetine can reduce pain associated with HZ, and therefore can have clinically relevant benefits. Clinical Trials Registration. Clinicaltrials.gov, NCT04313335. Registered on 18 March 2020.

Assessing herpes zoster vaccine efficacy in patients with diabetes: A community-based cohort study.

The effectiveness of herpes zoster (HZ) vaccines in patients with diabetes over the age of 50 remains an active area of research. Utilizing a real-world database from the US community, this study spanning from 2006 to 2023, aimed to evaluate the impact of HZ vaccination on newly diagnosed diabetes patients who received an HZ vaccination within 1 year of diagnosis. Exclusion criteria were established to omit patients with immune deficiencies. The cohort consisted of 53 885 patients, with an average age of 63.5 years, including 43% females and 58% whites. After implementing 1:1 propensity score matching for age, sex, race, comorbidities, diabetes medication, and hemoglobin A1c to ensure comparability, the study population was further stratified into four groups: N1 comparing any HZ vaccination to non-HZ vaccination (53 882 matched pairs), N2 for Shingrix versus non-HZ vaccination (16 665 matched pairs), N3 for Zostavax versus non-HZ vaccination (12 058 matched pairs), and N4 for Shingrix versus Zostavax (11 721 matched pairs). Cox proportional hazards regression analysis revealed a hazard ratio (HR) for HZ incidence post any HZ vaccination of 0.92 (95% confidence interval [CI]: 0.83-1.01). Additional analyses yielded HRs of 1.12 (95% CI: 0.93-1.34) for Shingrix versus non-HZ vaccine, 1.02 (95% CI: 0.86-1.20) for Zostavax versus non-HZ vaccine, and 1.06 (95% CI: 0.87-1.29) for Shingrix versus Zostavax. Subgroup analyses across age, sex, and follow-up duration also showed no significant differences. These findings underscore the lack of a significant benefit from HZ vaccination in newly diagnosed diabetes patients aged over 50, highlighting the necessity for further prospective research.

A systematic review and meta-analysis of herpes zoster occurrence/recurrence after COVID-19 infection and vaccination.

To inform surveillance, prevention, and management strategies for the varicella zoster virus (VZV) during the COVID-19 pandemic, this study aimed to evaluate the risk of herpes zoster (HZ) occurrence/recurrence following COVID-19 infection and vaccination. A comprehensive search across seven databases was conducted up to January 31, 2024, to identify studies relevant to the occurrence of HZ following COVID-19 infection and vaccination. The meta-analysis included five studies on postinfection HZ and 13 studies on postvaccination HZ. Patients infected with COVID-19 had a 2.16-fold increased risk of HZ (95% confidence interval [CI]: 1.24-3.76) than uninfected individuals. However, there was no significant association between COVID-19 vaccination and the risk of HZ compared to controls, with a relative risk (RR) of 1.08 (95% CI: 0.84-1.39). Furthermore, a descriptive analysis of 74 postinfection and 153 postvaccination HZ studies found no significant differences on gender or age (<50 and ≥50 years) following COVID-19 infection. Notably, 44.0% of the HZ cases postinfection appeared within the first week, with 69.5% resolving within 10 days, predominantly presenting as skin lesions. In the postvaccination group, the majority (60.1%) developed HZ after the first dose and 66.7% occurred within 1 week. Moreover, 44.6% resolved within 10 days and 50.0% within a month, primarily exhibiting skin lesions and postherpetic neuralgia. The study found that COVID-19 infection increases the risk of HZ, but the COVID-19 vaccine does not. Further study is needed to explore the association between COVID-19 and HZ.

The synergistic effect of insomnia and depression on risk of herpes zoster.

Sleep problems was associated with increased risk for herpes zoster (HZ). This study examined subjects with insomnia or a combination of insomnia and depression and their risk of HZ. This retrospective cohort study included a total of 47,256 participants, with a control comprising 31,504 age- and sex-matched patients. Clinical data from 2000 to 2013 in the Taiwan National Health Insurance Research Database were used for analysis. Insomnia, depression, and HZ were defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification. Subjects with insomnia had a significantly higher incidence of HZ (2.77 per 1000 person-years) than the controls (1.81 per 1000 person-years) as well as a higher risk of developing HZ (adjusted hazard ratio (AHR) = 1.62, 95% confidence interval (CI) = 1.35-1.93). Results shown subjects with insomnia durations of < 4 years, 4-6 years, and > 6 years had a significantly higher risk of HZ compared with the controls (AHR: 6.69, 95% CI 4.44-9.39; AHR: 4.42, 95% CI 3.07-6.36; AHR:1.38, 95% CI 1.14-1.87, respectively). We found a significantly higher risk of HZ in subjects with both insomnia and depression (AHR = 4.95; 95% CI = 3.99-7.02) than in those without related conditions. Patients with insomnia, and even more so those with comorbid depression, had a higher risk of developing HZ. This indicates a joint effect of insomnia and depression on HZ.

Common Features Between Stroke Following Varicella in Children and Stroke Following Herpes Zoster in Adults : Varicella-Zoster Virus in Trigeminal Ganglion.

The cerebral arteries are innervated by afferent fibers from the trigeminal ganglia. Varicella-zoster virus (VZV) frequently resides in the trigeminal ganglion. Reports of arterial ischemic stroke due to VZV cerebral vasculopathy in adults after herpes zoster have been described for decades. Reports of arterial ischemic stroke due to post-varicella cerebral arteriopathy in children have also been described for decades. One rationale for this review has been post-licensure studies that have shown an apparent protective effect from stroke in both adults who have received live zoster vaccine and children who have received live varicella vaccine. In this review, we define common features between stroke following varicella in children and stroke following herpes zoster in adults. The trigeminal ganglion and to a lesser extent the superior cervical ganglion are central to the stroke pathogenesis pathway because afferent fibers from these two ganglia provide the circuitry by which the virus can travel to the anterior and posterior circulations of the brain. Based on studies in pseudorabies virus (PRV) models, it is likely that VZV is carried to the cerebral arteries on a kinesin motor via gE, gI and the homolog of PRV US9. The gE product is an essential VZV protein.

A Guide to Preclinical Models of Zoster-Associated Pain and Postherpetic Neuralgia.

Reactivation of latent varicella-zoster virus (VZV) causes herpes zoster (HZ), which is commonly accompanied by acute pain and pruritus over the time course of a zosteriform rash. Although the rash and associated pain are self-limiting, a considerable fraction of HZ cases will subsequently develop debilitating chronic pain states termed postherpetic neuralgia (PHN). How VZV causes acute pain and the mechanisms underlying the transition to PHN are far from clear. The human-specific nature of VZV has made in vivo modeling of pain following reactivation difficult to study because no single animal can reproduce reactivated VZV disease as observed in the clinic. Investigations of VZV pathogenesis following primary infection have benefited greatly from human tissues harbored in immune-deficient mice, but modeling of acute and chronic pain requires an intact nervous system with the capability of transmitting ascending and descending sensory signals. Several groups have found that subcutaneous VZV inoculation of the rat induces prolonged and measurable changes in nociceptive behavior, indicating sensitivity that partially mimics the development of mechanical allodynia and thermal hyperalgesia seen in HZ and PHN patients. Although it is not a model of reactivation, the rat is beginning to inform how VZV infection can evoke a pain response and induce long-lasting alterations to nociception. In this review, we will summarize the rat pain models from a practical perspective and discuss avenues that have opened for testing of novel treatments for both zoster-associated pain and chronic PHN conditions, which remain in critical need of effective therapies.

Herpes Zoster and Risk of Incident Parkinson's Disease in US Veterans: A Matched Cohort Study.

BACKGROUND: Although some systemic infections are associated with Parkinson's disease (PD), the relationship between herpes zoster (HZ) and PD is unclear. OBJECTIVE: The objective is to investigate whether HZ is associated with incident PD risk in a matched cohort study using data from the US Department of Veterans Affairs. METHODS: We compared the risk of PD between individuals with incident HZ matched to up to five individuals without a history of HZ using Cox proportional hazards regression. In sensitivity analyses, we excluded early outcomes. RESULTS: Among 198,099 individuals with HZ and 976,660 matched individuals without HZ (median age 67.0 years (interquartile range [IQR 61.4-75.7]); 94% male; median follow-up 4.2 years [IQR 1.9-6.6]), HZ was not associated with an increased risk of incident PD overall (adjusted HR 0.95, 95% CI 0.90-1.01) or in any sensitivity analyses. CONCLUSION: We found no evidence that HZ was associated with increased risk of incident PD in this cohort. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The importance of immunization in cancer prevention, treatment, and survivorship.

Answer questions and earn CME/CNE A measles outbreak originating in California during 2014 and 2015 called attention to the potential for infectious disease outbreaks related to underimmunized populations in the United States and the potential risk to pediatric patients with cancer attending school when such outbreaks occur. Compliance with vaccine recommendations is important for the prevention of hepatitis B-related and human papillomavirus-related cancers and for protecting immunocompromised patients with cancer, and these points are often overlooked, resulting in the continued occurrence of vaccine-preventable neoplastic and infectious diseases and complications. This article provides an overview of the importance of vaccines in the context of cancer and encourages clinician, health system, and public policy efforts to promote adherence to immunization recommendations in the United States. CA Cancer J Clin 2017;67:398-410. © 2017 American Cancer Society.

Associations between organic erectile dysfunction and the risk of herpes zoster and postherpetic neuralgia in men.

BACKGROUND: Whether erectile dysfunction (ED) leads to considerable stress for affected men remains unclear? In this study, we investigated whether organic ED (OED) is associated with increased risks of herpes zoster (HZ) and postherpetic neuralgia (PHN). METHODS: A representative subset of Taiwan's National Health Insurance Research Database was employed for this study. Enrollees with OED from the years 2000 to 2018 were selected. To ensure comparability between the case and control groups, we implemented 1:1 propensity score matching based on age, index year, comorbidities, and medications. RESULTS: The case group included 20,808 patients with OED, while the control group consisted of 20,808 individuals without OED. The OED group exhibited a significantly elevated risk of HZ (adjusted hazard ratio [aHR] = 1.74) and PHN (aHR = 1.56) compared to the non-OED group. CONCLUSIONS: Men experiencing OED seem to face elevated risks of HZ and PHN compared to those without OED. ED may serve as a warning sign for individuals at HZ risk.

Risk factors for herpes zoster infections: a systematic review and meta-analysis unveiling common trends and heterogeneity patterns.

PURPOSE: The burden of herpes zoster (HZ) is substantial and numerous chronic underlying conditions are known as predisposing risk factors for HZ onset. Thus, a comprehensive study is needed to synthesize existing evidence. This study aims to comprehensively identify these risk factors. METHODS: A systematic literature search was done using MEDLINE via PubMed, EMBASE and Web of Science for studies published from January 1, 2003 to January 1, 2023. A random-effects model was used to estimate pooled Odds Ratios (OR). Heterogeneity was assessed using the I2 statistic. For sensitivity analyses basic outlier removal, leave-one-out validation and Graphic Display of Heterogeneity (GOSH) plots with different algorithms were employed to further analyze heterogeneity patterns. Finally, a multiple meta-regression was conducted. RESULTS: Of 6392 considered records, 80 were included in the meta-analysis. 21 different conditions were identified as potential risk factors for HZ: asthma, autoimmune disorders, cancer, cardiovascular disorders, chronic heart failure (CHF), chronic obstructive pulmonary disorder (COPD), depression, diabetes, digestive disorders, endocrine and metabolic disorders, hematological disorders, HIV, inflammatory bowel disease (IBD), mental health conditions, musculoskeletal disorders, neurological disorders, psoriasis, renal disorders, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and transplantation. Transplantation was associated with the highest risk of HZ (OR = 4.51 (95% CI [1.9-10.7])). Other risk factors ranged from OR = 1.17-2.87, indicating an increased risk for all underlying conditions. Heterogeneity was substantial in all provided analyses. Sensitivity analyses showed comparable results regarding the pooled effects and heterogeneity. CONCLUSIONS: This study showed an increased risk of HZ infections for all identified factors.

Guillain-Barre syndrome of acute motor axonal neuropathy (AMAN) type associated with herpes zoster: a case report.

Guillain Barre syndrome (GBS) following Varicella zoster is a rare presentation and has only been reported in a few cases around the world. Of the reported cases, the type of GBS is not specified in the majority, and where specified is of the acute inflammatory demyelinating polyradiculoneuropathy (AIDP) type. We report a case of acute motor axonal neuropathy (AMAN) type GBS following herpes zoster in a 27-year-old male who presented with bilateral lower limb weakness and left sided lower motor neuron type facial nerve palsy a week after herpes zoster infection.

Neuralgia in the occipital region associated with ipsilateral trigeminal herpes zoster: Three case reports.

BACKGROUND: Nerve fibers related to pain and temperature sensation in the trigeminal nerve territory converge with the upper cervical spinal nerves from the level of the lower medulla oblongata to the upper cervical cord. This structure is called the trigemino-cervical complex and may cause referred pain in the territory of the trigeminal or upper cervical spinal nerves. CASE SERIES: Here, we report three cases of paroxysmal neuralgia in the occipital region with mild conjunctivitis or a few reddish spots in the ipsilateral trigeminal nerve territory. The patients exhibited gradual progression of these reddish spots evolving into vesicles over the course of several days, despite the absence of a rash in the occipital region. The patients were diagnosed with trigeminal herpes zoster and subsequently received antiherpetic therapy. Remarkably, the neuralgia in the occipital region showed gradual amelioration or complete resolution before the treatment, with no sequelae reported in the occipital region. DISCUSSION: The trigemino-cervical complex has the potential to cause neuralgia in the occipital region, as referred pain, caused by trigeminal herpes zoster. These cases suggest that, even if conjunctivitis or reddish spots appear to be trivial in the trigeminal nerve territory, trigeminal herpes zoster should be considered when neuralgia occurs in the ipsilateral occipital region.

Herpes zoster (HZ) vaccine coverage and confidence in Italy: a Nationwide cross-sectional study, the OBVIOUS project.

BACKGROUND: Herpes Zoster is an age dependent disease and as such it represents a problem in the Italian social context, where the demographic curve is characterized by an overrepresentation of the elderly population. Vaccines against Herpes Zoster are available, safe and effective, however coverage remains sub-optimal. This study was therefore conducted to examine the variations in Herpes Zoster vaccine uptake and confidence across different regions in Italy. METHODS: This study utilized a cross-sectional computer-assisted web interview (CAWI) methodology. The survey was conducted by Dynata, an online panel provider, and involved 10,000 respondents recruited in Italy between April 11 and May 29, 2022. The sample was stratified based on geographic region, gender, and age group. Data management adhered to European Union data protection regulations, and the survey covered demographics, living conditions, and vaccination against herpes zoster (HZ), following the BeSD framework. RESULTS: The findings indicate regional disparities in herpes zoster vaccine uptake across Italy. Notably, the Islands region exhibits a particularly low vaccination rate (2.9%), highlighting the need for targeted interventions. The multivariate regression analysis showed that sociodemographic factors, limited access to healthcare services, and inadequate awareness of vaccine eligibility contribute to the lower uptake observed in this region. CONCLUSION: In conclusion, this research emphasizes regional disparities in herpes zoster (HZ) vaccination uptake in Italy. Demographic, socioeconomic, and geographic factors impact individuals' willingness to receive the vaccine. The study highlights the importance of awareness of vaccine eligibility and accessible vaccination facilities in increasing uptake rates.

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).