Zoster Vaccine Research Articles

Systematic review and network meta-analysis of the risk of Herpes zoster with biological therapies and selective Janus kinase-1 inhibitors in atopic dermatitis.

Atopic dermatitis (AD) patients have an increased risk of herpes zoster (HZ). The relationship of dupilumab, tralokinumab, upadacitinib, and abrocitinib to HZ incidence in AD patients remains unclear. To evaluate and compare the incidence and risk of HZ among patients with moderate to severe atopic dermatitis treated with advanced systemic therapies. Systematic searches were conducted in Ovid Medline and Embase. The primary outcome was incidence of HZ in patients with moderate to severe AD receiving placebo or the aforementioned treatments. A frequentist random-effects NMA was conducted with odds ratio. Our search identified 16 trials comprising 10,689 patients. Upadacitinib was associated with a dose-dependent increase in the incidence of HZ compared to placebo (OR = 2.55 [1.09, 5.95] and (OR = 4.29 [1.89, 9.74], respectively) and compared to various dupilumab doses (OR = 4.48 [1.29, 15.57], 3.61 [1.28, 10.18] and 7.54 [2.21, 25.68], 6.09 [2.24, 16.52], respectively). Upadacitinib 30 mg was associated with a higher incidence of HZ when compared to upadacitinib 15 mg (OR = 1.68 [1.19, 2.38]). Abrocitinib 200 mg was associated with a higher increase in HZ compared to placebo (OR = 3.34 [1.34, 8.31]). According to SUCRA ranks, both JAK-1 inhibitors had a higher cumulative incidence of HZ compared to dupilumab. JAK-1 inhibitors are associated with a significantly higher incidence of HZ compared to dupilumab and placebo. Our results suggest that recombinant HZ vaccination should be highly considered for all adult patients prior to starting oral JAK-1 inhibitors.

Acute psoriasis exacerbation by recombinant zoster vaccine: a case report

Acute psoriasis exacerbation by recombinant zoster vaccine: a case report

A Synergistic Lipid Nanoparticle Encapsulating mRNA Shingles Vaccine Induces Potent Immune Responses and Protects Guinea Pigs from Viral Challenges.

Shingles is caused by the reactivation of varicella zoster virus (VZV) and manifests as painful skin rashes. While the recombinant protein-based vaccine proves highly effective, it encounters supply chain challenges due to a shortage of the necessary adjuvant. Messenger RNA (mRNA)-based vaccines can be rapidly produced on a large scale, but their effectiveness relies on efficient delivery and sequence design. Here, an mRNA-based VZV vaccine using a synergistic lipid nanoparticle (Syn-LNP) containing two different ionizable lipids is developed. Syn-LNP shows superior mRNA expression compared to LNPs formulated with either type of ionizable lipid and to a commercialized LNP. After encapsulating VZV glycoprotein E (gE)-encoding mRNA, mgE@Syn-LNP induces robust humoral and cellular immune responses in two strains of mice. The magnitude of these responses is similar to that induced by adjuvanted recombinant gE proteins and significantly higher than that observed with live-attenuated VZV. mgE@Syn-LNP exhibits durable humoral responses for over 7 months without obvious adverse effects. In addition, mgE@Syn-LNP protects vaccinated guinea pigs against live VZV challenges. Preliminary studies on the mRNA antigen design reveal that the removal of glycosylation sites of gE greatly reduces its immune responses. Collectively, Syn-LNP encapsulating gE-encoded mRNA holds great promise as a shingles vaccine.

PROTECTIVE EFFECT OF SHINGLES VACCINE ON ALZHEIMER’S DISEASE CAN BE MODULATED BY RISK VARIANT OF NECTIN2 GENE

Abstract The aging-related decline in immune surveillance was suggested to play a major role in Alzheimer’s disease (AD). Adult vaccinations may support the aging immune system beyond prevention of the target disease, and through this provide a protection against AD. Such off-target effects of vaccines may potentially be affected by genetic risk factors for AD. To explore this possibility, we estimated association of the vaccination against shingles (reactivated herpes zoster virus infection) received between ages 65-75 with AD onset at ages 75+ in the Health and Retirement Study (HRS) survey participants, comparing the carriers and non-carriers of rs6859 A allele of NECTIN2 gene (AD risk factor that is also involved in vulnerability to viral infections). We used logistic regression model with covariates including sex, race, education, and smoking status. We found that shingles vaccine was significantly associated with lower odds of AD onset later in life, in the total sample (p-value=0.021; OR=0.55 (0.33, 0.92)). After stratification by genotype, the protective effect of vaccine became stronger in rs6859 A carriers (p-value=0.016; OR=0.44 (0.22, 0.86)), but disappeared in the non-carriers, for both significance and size (p-value=0.81; OR=0.90). We conclude that adult shingles vaccine may reduce chances of AD at older ages, and this effect appears more beneficial for carriers of rs6859 A allele of NECTIN2 gene. Repurposing of existing vaccines may benefit the aging immune system, and be a promising approach to personalized genotype-tailored prevention of AD.

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.

Knowledge About the Herpes Zoster (HZ) Vaccine and Its Acceptance Among the Population in Al-Ahsa City in the Kingdom of Saudi Arabia.

Introduction Herpes zoster (HZ), caused by the varicella-zoster virus (VZV), poses a public health concern in Saudi Arabia, with an increasing number of cases reported in recent years. This study aimed to assess the knowledgeand acceptance of the herpes zoster vaccine among Saudi Arabian citizens in Al-Ahsa. Methodology A descriptive cross-sectional study was conducted using online surveys administered via social media platforms. The study was conducted in Al-Ahsa, a city located in the Eastern Province of Saudi Arabia. Al-Ahsa serves as a representative urban area within Saudi Arabia. Result The study found a high level of awareness and knowledge about the vaccine, with 78.2% of the participants having heard of herpes zoster. The majority considered the vaccine effective (89%) and believed it was available in Saudi Arabia (87%). However, the vaccination rate was only 8%. The study revealed varied opinions on the target population for vaccination, with 39.7% favoring immunocompromised patients and 38.1% choosing individuals above 50 years. The reasons for not being vaccinated included a lack of information (38.3%) and the belief of being in good health (37.3%). Conclusion The findings suggest a need for targeted educational campaigns to address misconceptions and promote vaccination, particularly among healthcare providers and the recommended target populations. Future research should explore barriers to vaccination to inform tailored interventions.

Adjuvant AS01 activates human monocytes for costimulation and systemic inflammation

BackgroundThe adjuvanted recombinant zoster vaccine (RZV) is highly effective even in adults over 80 years old. The high efficacy of RZV is attributed to its highly reactogenic adjuvant, AS01, but limited studies have been done on AS01’s activation of human immune cells. MethodsWe stimulated peripheral blood mononuclear cells (PBMC) with AS01 and used flow cytometry and RNA Sequencing (RNAseq) to analyze the impacts on human primary cells. ResultsWe found that incubation of PBMC with AS01 activated monocytes to a greater extent than any other cell population, including dendritic cells. Both classical and non-classical monocytes demonstrated this activation. RNASeq showed that TNF-ɑ and IL1R pathways were highly upregulated in response to AS01 exposure, even in older adults. ConclusionsIn a PBMC co-culture, AS01 strongly activates human monocytes to upregulate costimulation markers and induce cytokines that mediate systemic inflammation. Understanding AS01’s impacts on human cells opens possibilities to further address the reduced vaccine response associated with aging.

Impact of pharmacist interventions on immunisation uptake: a systematic review and meta-analysis.

Under-utilisation of immunisation services remains a public health challenge. Pharmacists act as facilitators and increasingly as immunisers, yet relatively little robust evidence exists of the impact elicited on patient health outcome and vaccination uptake. To evaluate the influence of pharmacist interventions on public vaccination rate. SCOPUS, PubMed, and Web of Science were searched from inception to April 2023 to retrieve non- and randomised controlled clinical trials (RCTs). Studies were excluded if no comparator group to pharmacist involvement was reported. Data extraction, risk of bias assessments, and meta-analyses using random-effect models, were performed. Four RCTs and 15 non-RCTs, encompassing influenza, pneumococcal, herpes zoster, and tetanus-diphtheria and pertussis vaccine types, and administered in diverse settings including community pharmacies, were included. Pooled effect sizes revealed that, as compared to usual care, pharmacists, regardless of their intervention, improved the overall immunisation uptake by up to 51% [RR 1.51 (1.28, 1.77)] while immunisation frequency doubled when pharmacists acted specifically as advocators [RR 2.09 (1.42, 3.07)]. While the evidence for pharmacist immunisers was mixed, their contribution to immunisation programmes boosted public vaccination rate. Pharmacists demonstrated leadership and acquired indispensable advocator roles in the community and hospital settings. Future research could explore the depth of engagement and hence the extent of influence on immunisation uptake.

Progressive shingles in a toddler due to reactivation of Varicella Zoster vaccine virus four days after infection with SARS-CoV-2; a case report

BackgroundHerpes zoster (HZ) is the clinical syndrome associated with reactivation of latent varicella-zoster virus (VZV). Several factors have been implicated to promote VZV reactivation; these include immunosuppression, older age, mechanical trauma, physiologic stress, lymphopenia, and more recently, infection with severe acute respiratory syndrome coronavirus-2 (SARS- CoV-2). Recent reports suggest an increase in the number of HZ cases in the general population during the global COVID-19 pandemic. However, it is unknown what proportion of HZ during the pandemic is due to reactivation of wild-type or vaccine-strain VZV.CaseHere we report the first known case of HZ concomitant with SARS-CoV2 infection in a 20-month-old female who was treated with a single dose of dexamethasone, due to reactivation of the vaccine-type strain of VZV after presenting with a worsening vesicular rash.ConclusionIn this case, we were able to show vaccine-strain VZV reactivation in the context of a mild acute symptomatic COVID-19 infection in a toddler. Being able to recognize HZ quickly and effectively in a pediatric patient can help stave off the significant morbidity and mortality associated with disease process.

Analysis of adult vaccination in Shandong Province from 2018 to 2022

Objective: To analyze the utilization of adult vaccination among people aged 18 and above in Shandong Province from 2018 to 2022. Methods: Data on vaccination units in 2022 and individual cases of vaccination information for people aged 18 and above were extracted from the Shandong Immunization Information System. A descriptive analysis was conducted on the distribution of adult vaccination units and adult vaccination varieties. The total vaccination amount and vaccination rate were calculated. Results: By the end of 2022, there were 3 948 vaccination units providing adult vaccination in Shandong Province, with 0.36 adult vaccination clinics per 10 000 people. Adult vaccination including RabV(rabies vaccine for human use), InfV(influenza vaccine), HPV(human papillomavirus), HepB(hepatitis B vaccine), PPV23(23-valent pneumococcal polysaccharide vaccine), MenACYW135(meningococcal polysaccharide vaccine group ACYW135), MMR(measles, mumps and rubella combined attenuated live vaccine), HEV(hepatitise E vaccine), RZV(recombinant zoster vaccine), TV(tetanus vaccine) and HF(haemorrhagic fever with renal syndrome vaccine) vaccines were administered, with a cumulative dose of 40.056 9 million and an average of 0.1 doses per person per year from 2018 to 2022. The top three vaccines were RabV, InfV and HPV, accounting for 31.48%, 22.57%, and 15.93% of the total vaccination amount, respectively. The annual vaccination dose for adults increased from 3.477 3 million in 2018 to 13.308 6 million in 2022, with an average annual growth rate of 56.55%. The cumulative 5-year doses of RabV and TV were 15.90 doses per 100 people and 0.21 doses per 100 people. The average annual vaccination rate of InfV was 2.28%. The cumulative full vaccination rates of HPV, HepB, PPV23 and RZV were 12.44%, 1.61%, 0.52% and 0.17%, respectively. The cumulative 5-year doses of RabV and TV were 29.19 doses per 100 people and 0.43 doses per 100 people in the age group of 20 to<30 years old. The vaccination rates of InfV and PPV23 were 9.08% and 1.27% in the age group of 70 to<80 years old. The vaccination rate of RZV was 0.11% in the age group of 50 to<60 years old. The HPV vaccination rate was 18.09% in the age group of 20 to<30 years old, and the HepB, MenACYW135, MMR and HEV vaccination rates were 6.21%, 9.55%, 2.65%, and 2.83% in the 18-19 age group, respectively. Conclusion: There are relatively few types of adult vaccination in Shandong Province, with narrow coverage and low vaccination rates.

Barriers to vaccination among older adults: Demographic variation and links to vaccine acceptance

BackgroundDespite risks of vaccine-preventable infectious diseases, many older adults are under vaccinated. The present study investigates possible barriers to acceptance of vaccines recommended for older adults and considers demographic variation and links to acceptance for distinct vaccines. MethodsA mailed survey was conducted with 901 older adults (aged 65+) across the state of North Dakota, oversampling for rural regions. The survey addressed demographic characteristics, barriers to vaccination (including needle phobia, cost, lacking doctor recommendation, transportation, and scheduling uncertainty), and vaccine acceptance (including provider guidance acceptance and uptake for influenza, shingles, pneumococcal, and COVID-19 vaccines). ResultsCost (27.2 %) and needle phobia (24.1 %) were the most prevalent barriers. Rural, lower educated, non-white, and living alone older adults experienced increased risks of barriers such as cost, lacking a doctor recommendation, transportation, and uncertainty how to schedule. Cost was associated with shingles vaccine uptake, whereas lacking doctor recommendation was associated with uptake for all vaccines except shingles. Needle phobia was associated with uptake of all vaccines except COVID-19. Transportation barrier was only associated with pneumococcal vaccine uptake. ConclusionsThese findings highlight relatively low prevalence of barriers, yet variability by older adults’ demographic characteristics. Further, the influence of barriers on acceptance varied by vaccine type. By better understanding the nuanced role of barriers to older adults’ vaccination, strategies to increase vaccination rates can be developed.

Recruitment of naive CD4+ T cells by the recombinant zoster vaccine correlates with persistent immunity.

Herpes zoster (HZ) is a substantial problem for people with decreased cell-mediated immunity, including older adults. The first vaccine approved for HZ prevention, the zoster vaccine live (ZVL), which provided limited and short-lived protection, has been supplanted by the superior recombinant zoster vaccine (RZV), which provides robust and durable protection. To understand the mechanisms underlying the differential immunologic characteristics of the 2 vaccines, we used T cell receptor β chain sequencing and peptide-MHC class II tetramer staining to analyze recombinant glycoprotein E-specific (gE-specific) CD4+ T cell clonotypes in RZV and ZVL recipients. Compared with ZVL, RZV expanded more gE-specific CD4+ clonotypes, with greater breadth and higher frequency of public clonotypes. RZV recruited a higher proportion of clonotypes from naive than from memory cells, while ZVL recruited equally from memory and naive compartments. Compared with memory-derived, naive-derived clonotypes were more likely to last 5 or more years after immunization. Moreover, the frequency of tetramer+ persistent clones correlated with the frequency of tetramer+ naive CD4+ prevaccination T cells. We conclude that the ability of RZV to recruit naive CD4+ T cells into the response may contribute to the durability of its effect. The abundance, breadth, and frequency of public clonotypes may further add to its protective effect.

Willingness to vaccinate against herpes zoster in Chinese urban population: a mixed-methods study

ObjectiveAlthough the herpes zoster vaccine has been available in mainland China since June 2020, residents’ knowledge of herpes zoster and the herpes zoster vaccine is poor, and vaccination rates are...

Herpes zoster vaccination prevents or delays dementia: causal evidence from a country‐wide natural experiment in Wales

AbstractBackgroundThere is growing recognition that infectious agents, particularly herpesviruses, could play a role in the development of some types of dementia.MethodIn Wales, eligibility for the herpes zoster vaccine (Zostavax) for shingles prevention was determined based on an individual’s exact date of birth. Those born before September‐2‐1933 were ineligible (and remained ineligible for life), while those born on or after September‐2‐1933 were eligible. This natural experiment provides causal, as opposed to correlational, evidence because there is no plausible reason why adults born just one week apart should differ systematically from each other. We used a regression discontinuity design in Welsh country‐wide data on primary and secondary care encounters, and death certificates. The outcome was a new dementia diagnosis as recorded in any of these data sources.ResultWe included 282,541 individuals born between September‐1‐1925 and August‐31‐1941. The percentage who received the zoster vaccine increased from 0.01% among those one week too old to be eligible, to 47.2% among those one week younger. Receiving the vaccine reduced the probability of a new dementia diagnosis over a follow‐up period of seven years by 3.5 percentage points (95% CI: 0.6‐7.1, p = 0.019), corresponding to a 22.4% relative decrease. There were significant protective effects from the vaccine for Alzheimer’s disease but not vascular dementia. Effects were far stronger among women than men. To demonstrate that our approach is causal, we show that i) there were no differences in pre‐existing conditions or uptake of other preventive interventions across the date‐of‐birth eligibility cutoff; ii) the zoster vaccine had no effects on any other common causes of morbidity and mortality; and iii) no other interventions used the same date‐of‐birth eligibility cutoff.ConclusionIn addition to identifying a readily available preventive intervention for dementia, our findings strongly suggest an important role of the varicella zoster virus in the etiology of dementia, particularly among women. Unlike existing studies in this field, this analysis provides causal evidence because individuals who differ in age by just one week are exchangeable with each other on both observed and unobserved characteristics, except for a large difference in the probability of receiving the zoster vaccine.

Advances in understanding the mechanism of action of adult vaccines.

The occurrence of herpes zoster (HZ) correlates with declining memory T cells that had responded to earlier infection with varicella-zoster virus (VZV). There are especially lower T cell responses to the single immunodominant VZV protein glycoprotein E (gE) in people over 50 years of age, although antibody responses to VZV persist. Therefore, a live attenuated zoster vaccine (ZVL) aimed at restoring T cell responses was developed. Surprisingly, a recombinant zoster vaccine (RZV) consisting of gE combined with the AS01B adjuvant system proved superior in efficacy and durability. In this issue of the JCI, Laing, Ford, and colleagues showed that both vaccines stimulated preimmunization naive CD4+ T cells, not just memory CD4+ T cells, to gE, and recruited these naive responses into the overall memory response. However, compared with ZVL, RZV stimulated this response to a much greater degree. These results will help guide development of more effective and durable vaccines for older individuals.

Vaccination in old age: an overview

Vaccinations against infectious diseases are ahighly effective preventive measure, especially in old age due to the higher susceptibility to infections. As the effectiveness of vaccinations decreases in old age due to immune senescence but also due to comorbidities, specific, more immunogenic vaccines have been developed for this target group. In Germany, the Standing Commission on Vaccination (STIKO) publishes annually updated vaccination recommendations also specifically for the 60+ years age group. Since 2018, standard vaccinations for this group have included herpes zoster vaccination with adjuvanted inactivated vaccine. Since 2021, the use of the quadrivalent influenza high-dose vaccine is recommended for this age group. Currently, the annual COVID-19 vaccination and the single pneumococcal vaccination with the new 20-valent conjugate vaccine have been added as standard vaccinations. The free STIKO app provides an always up to date overview of standard and indicated vaccinations for all age groups.

EPH156 Modelling Herpes Zosters Burden and Public Health Impact of Adjuvanted Recombinant Zoster Vaccine Among Adults Aged ≥50 Years Old in Seven Countries in Central and South America

EPH156 Modelling Herpes Zosters Burden and Public Health Impact of Adjuvanted Recombinant Zoster Vaccine Among Adults Aged ≥50 Years Old in Seven Countries in Central and South America

S15 Recombinant Zoster Vaccine (RZV) is Effective in Reducing Herpes Zoster Infection in Patients With Inflammatory Bowel Disease: A US Propensity Matched Cohort Study

S15 Recombinant Zoster Vaccine (RZV) is Effective in Reducing Herpes Zoster Infection in Patients With Inflammatory Bowel Disease: A US Propensity Matched Cohort Study

EE292 Cost Effectiveness Analysis of Recombinant Zoster Vaccine Among 50 Years Old and Older in Sweden

EE292 Cost Effectiveness Analysis of Recombinant Zoster Vaccine Among 50 Years Old and Older in Sweden

EE294 Public Health Impact and Cost-Effectiveness of Recombinant Zoster Vaccination Among 50 Years Old or Older in Austria

EE294 Public Health Impact and Cost-Effectiveness of Recombinant Zoster Vaccination Among 50 Years Old or Older in Austria