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.

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.

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).

Knowledge, Attitudes and Practices Survey of Recombinant Zoster Vaccine among Cardiologists and Cardiac Nurses in Italy.

Background and Objectives: Cardiac patients are particularly at risk of herpes zoster (HZ), which is associated with a higher risk of major cardiovascular events. This research aimed to analyze the knowledge, attitudes and practices towards recombinant zoster vaccine (RZV) among cardiac healthcare professionals (HPs). Materials and Methods: A cross-sectional survey was conducted in a cardiological hospital in Italy. Multivariate regression models were built to identify factors associated with the outcomes of interest. Results: The response rate was 78.2% (154/197). Overall, age > 50 years and immunosuppression were recognized as risk factors for HZ by 38.3% and 75.3% of respondents, respectively. Regarding RZV, 29.1% of the HPs correctly responded about its schedule and 57.6% about the possibility of administration in immunocompromised individuals. This knowledge was significantly higher in HPs with a higher educational level (odds ratio (OR) = 4.42; 95%CI 1.70-11.47), in those who knew that HZ could cause postherpetic neuralgia (OR = 2.56; 95%CI 1.05-6.25) or major cardiovascular events (OR = 4.23; 95%CI 1.50-11.91), in those who had participated in professional updates on vaccinations (OR = 3.86; 95%CI 1.51-9.87) and in those who stated the need for further information about the RZV (OR = 6.43; 95%CI 1.42-29.98). Younger HPs (coefficient (ß) = -0.02; 95%CI -0.04--0.01), those with a positive attitude toward RZV safety (ß = 2.92; 95%CI 2.49-3.36) and those who had previously cared for patients with HZ (ß = 0.45; 95%CI 0.03-0.88) reported a more positive attitude toward RZV effectiveness. The practice of recommending vaccination was more prevalent in younger HPs (OR = 0.94; 95%CI 0.89-0.99), in those who had a master's degree or higher education (OR = 7.21; 95%CI 1.44-36.08), in those with more positive attitudes toward RZV effectiveness (OR = 7.17; 95%CI 1.71-30.03) and in HPs who had already recommended the vaccine to patients in the past (OR = 4.03; 95%CI 1.08-14.96). Conclusions: Despite being a single-center study, our research brings attention to factors that currently impact cardiac HPs' approaches to RZV. The findings indicate potential measures to enhance HPs' awareness and practices, ultimately aiming to improve vaccination adherence and reduce the burden associated with HZ.

No Immunological Interference or Safety Concerns When Adjuvanted Recombinant Zoster Vaccine Is Coadministered With a Coronavirus Disease 2019 mRNA-1273 Booster Vaccine in Adults Aged 50 Years and Older: A Randomized Trial.

BACKGROUND: There is growing consensus that coronavirus disease 2019 booster vaccines may be coadministered with other age-appropriate vaccines. Adding to the limited available data supporting coadministration, especially with adjuvanted vaccines, could enhance vaccine coverage in adults. METHODS: In this phase 3, randomized, open-label study, eligible adults aged ≥50 years were randomly assigned (1:1) to receive mRNA-1273 (50 µg) booster vaccination and a first dose of recombinant zoster vaccine (RZV1) 2 weeks apart (Seq group) or concomitantly (Coad group). The second RZV dose (RZV2) was administered 2 months post-RZV1 in both groups. Primary objectives were noninferiority of anti-glycoprotein E (gE) and anti-spike protein antibody responses in the Coad group compared to the Seq group. Safety and further immunogenicity assessments were secondary objectives. RESULTS: In total, 273 participants were randomized to the Seq group and 272 to the Coad group. Protocol-specified noninferiority criteria were met. The adjusted geometric mean concentration ratio (Seq/Coad) was 1.01 (95% confidence interval [CI], .89-1.13) for anti-gE antibodies 1 month post-RZV2, and 1.09 (95% CI, .90-1.32) for anti-spike antibodies 1 month post-mRNA-1273 booster. No clinically relevant differences were observed in overall frequency, intensity, or duration of adverse events between the 2 study groups. Most solicited adverse events were mild/moderate in intensity, each with median duration ≤2.5 days. Administration site pain and myalgia were the most frequently reported in both groups. CONCLUSIONS: Coadministration of mRNA-1273 booster vaccine with RZV in adults aged ≥50 years was immunologically noninferior to sequential administration and had a safety and reactogenicity profile consistent with both vaccines administered sequentially. Clinical Trials Registration. NCT05047770.

Active Postlicensure Safety Surveillance for Recombinant Zoster Vaccine Using Electronic Health Record Data.

Recombinant zoster vaccine (RZV) (Shingrix; GlaxoSmithKline, Brentford, United Kingdom) is an adjuvanted glycoprotein vaccine that was licensed in 2017 to prevent herpes zoster (shingles) and its complications in older adults. In this prospective, postlicensure Vaccine Safety Datalink study using electronic health records, we sequentially monitored a real-world population of adults aged ≥50 years who received care in multiple US Vaccine Safety Datalink health systems to identify potentially increased risks of 10 prespecified health outcomes, including stroke, anaphylaxis, and Guillain-Barré syndrome (GBS). Among 647,833 RZV doses administered from January 2018 through December 2019, we did not detect a sustained increased risk of any monitored outcome for RZV recipients relative to either historical (2013-2017) recipients of zoster vaccine live, a live attenuated virus vaccine (Zostavax; Merck & Co., Inc., Kenilworth, New Jersey), or contemporary non-RZV vaccine recipients who had an annual well-person visit during the 2018-2019 study period. We confirmed prelicensure trial findings of increased risks of systemic and local reactions following RZV. Our study provides additional reassurance about the overall safety of RZV. Despite a large sample, uncertainty remains regarding potential associations with GBS due to the limited number of confirmed GBS cases that were observed.

Disseminated vaccine-induced varicella infection in a kidney transplant recipient.

A 33-year-old kidney transplant (KT) recipient presented with a disseminated pruritic, painful, vesicular rash and hepatitis 3 weeks after receiving a varicella vaccine (VAR). A skin lesion biopsy sent to the Centers for Disease Control and Prevention for genotyping confirmed vaccine-strain varicella-zoster virus (VZV) (Oka strain; vOka). The patient was successfully treated with intravenous acyclovir during a prolonged hospital stay. This case supports the contraindication of VAR in adult KT recipients and highlights the potential for severe illness when used in this population. Optimally, VZV-seronegative KT candidates should receive VAR before starting immunosuppressive medications. If this opportunity is missed, the recombinant varicella-zoster vaccine might be considered following transplantation as it is already recommended to prevent herpes zoster in VZV-seropositive immunocompromised adults. Further study is needed as data are limited on the safety and efficacy of recombinant varicella-zoster vaccine for primary varicella prevention in VZV-seronegative immunocompromised adults.

Survey of Physician Practices, Attitudes, and Knowledge Regarding Recombinant Zoster Vaccine.

BACKGROUND: Herpes zoster vaccination rates remain low despite longstanding national recommendations to vaccinate immunocompetent adults aged ≥ 50 years. The Advisory Committee on Immunization Practice (ACIP) updated its recommendations for recombinant zoster vaccine (RZV) in October 2021 to include immunocompromised adults aged ≥19 years. OBJECTIVE: To assess practices, attitudes, and knowledge about RZV, barriers to recommending RZV, and likelihood of recommending RZV to patients with various immunocompromising conditions. DESIGN: Mail and internet-based survey conducted from May through July 2020. PARTICIPANTS: General internists and family physicians throughout the USA. MAIN MEASURES: Survey responses. KEY RESULTS: The response rate was 66% (632/955). Many physicians were already recommending RZV to immunocompromised populations, including adults ≥50 years with HIV (67% of respondents) and on recombinant human immune modulator therapy (56%). Forty-seven percent of respondents both stocked/administered RZV and referred patients elsewhere, frequently a pharmacy, for vaccination; 42% did not stock RZV and only referred patients. The majority agreed pharmacies do not inform them when RZV has been given (64%). Physicians were generally knowledgeable about RZV; however, 25% incorrectly thought experiencing side effects from the first dose of RZV that interfere with normal activities was a reason to not receive the second dose. The top reported barrier to recommending RZV was experience with patients declining RZV due to cost concerns (67%). Most physicians reported they would be likely to recommend RZV to immunocompromised patients. CONCLUSION: Most primary care physicians welcome updated ACIP RZV recommendations for immunocompromised adults. Knowledge gaps, communication issues, and financial barriers need to be addressed to optimize vaccination delivery.

Cost-Effectiveness Analysis of Vaccination With Recombinant Zoster Vaccine Among Hematopoietic Cell Transplant Recipients and Persons With Other Immunocompromising Conditions Aged 19 to 49 Years.

OBJECTIVES: This study aimed to estimate the cost-effectiveness of the use of recombinant zoster vaccine (RZV) (Shingrix), which protects against herpes zoster (HZ), among immunocompromised adults aged 19 to 49 years, as a contribution to deliberations of the Advisory Committee on Immunization Practices. METHODS: Hematopoietic cell transplant (HCT) recipients experience a high incidence of HZ, and the efficacy of RZV in preventing HZ has been studied in clinical trials. The cost-effectiveness model calculated incremental cost-effectiveness ratios that compared vaccination with RZV with a no vaccination strategy among adults aged 19 to 49 years. Costs and outcomes were calculated until age 50 years using the healthcare sector perspective and summarized as cost per quality-adjusted life-year (QALY) gained. The base case represents HCT recipients, with scenario analyses representing persons with other immunocompromising conditions, including hematologic malignancies, human immunodeficiency virus, and autoimmune and inflammatory conditions. Uncertainty was investigated using univariate, multivariate, and probabilistic sensitivity analyses. RESULTS: Base-case results indicated vaccination with RZV would avert approximately 35% of HZ episodes and complications, while saving approximately 11% of net costs. Compared with no vaccination, vaccination of HCT recipients with RZV generated cost-savings (ie, lower costs and improved health) in the base case and in 81% of simulations in the probabilistic analysis. In scenario analyses, vaccination cost US dollar ($) 9500/QALY among patients with hematologic malignancies, $79 000/QALY among persons living with human immunodeficiency virus, and $208 000/QALY among persons with selected autoimmune and inflammatory conditions. CONCLUSIONS: Generally favorable economic estimates supported recommendations for vaccination of immunocompromised adults with RZV to prevent episodes of HZ and related complications.

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).

Epidemiology of Herpes Zoster in the pre-vaccination era: establishing the baseline for vaccination programme's impact in Spain.

BackgroundHerpes zoster (HZ) affects 1 in 3 persons in their lifetime, and the risk of HZ increases with increasing age and the presence of immunocompromising conditions. In Spain, vaccination guidelines were recently updated to include the recommendation of the new recombinant zoster vaccine (RZV) for certain risk groups.AimTo describe the epidemiology of HZ-related hospitalisations in Spain in order to prioritise vaccination recommendations and define a baseline to monitor the effectiveness of vaccination policies.MethodsRetrospective study using the National Health System's Hospital Discharge Records Database, including all HZ-related hospitalisations from 1998 to 2018.ResultsThe 65,401 HZ-related hospitalisations, corresponded to an annual mean hospitalisation rate of 6.75 per 100,000 population. There was an increasing trend of HZ hospitalisations over the study period. This rate was higher in males and older age groups, particularly over 65 years. Comorbidities with higher risk of readmission were leukaemia/lymphoma (RR 2.4; 95% CI: 2.3-2.6) and solid malignant neoplasm (RR 2.2; 95% CI: 2.1-2.4). Comorbidities associated with higher risk of mortality were leukaemia/lymphoma (RR 2.9; 95% CI: 2.7-3.2), solid malignant neoplasm (RR 2.9; 95% CI: 2.7-3.1) and HIV infection (RR 2.2; 95% CI: 1.8-2.7).ConclusionOf all patients hospitalised with HZ, those with greater risk of mortality or readmission belonged to the groups prioritised by the current vaccination recommendations of the Spanish Ministry of Health. Our study provided relevant information on clinical aspects of HZ and established the base for future assessments of vaccination policies.

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.

Factors influencing herpes zoster vaccination among older people in China: results from a discrete choice experiment.

OBJECTIVES: Vaccination is the most effective way to prevent herpes zoster (HZ) and related complications. This study aimed to investigate the preference of HZ vaccine among older people. STUDY DESIGN: A discrete choice experiment was performed. METHODS: In total, 178 adults aged ≥50 years were invited to choose between HZ vaccination scenarios using six vaccine attributes. Two equations were used to calculate participants' willingness to pay for the vaccine and their predicted choice probability. RESULTS: The attributes that significantly influenced participants' vaccine choices were lower cost, higher effectiveness, reduced side-effects and vaccination of others in their surroundings. CONCLUSIONS: Improving medical insurance coverage or reducing the cost of the HZ vaccine will encourage more people to be vaccinated, resulting in reduced burden of disease among older people.

Vaccination coverage and predictors of influenza, pneumococcal, herpes zoster, tetanus, measles, and hepatitis B vaccine uptake among adults in Greece.

OBJECTIVES: Insufficient adult vaccination coverage rates remain an international challenge. This nationwide study aimed at exploring vaccination coverage and predictors of influenza, pneumococcal, herpes zoster, tetanus, measles, and hepatitis B vaccine uptake, following the recommendations of the National Immunization Program for adults. STUDY DESIGN: This was a multicenter, mixed-methods study conducted at 23 primary care units in six different regions of Greece. METHODS: A pretested questionnaire was administered to three randomly selected adults who visited each practice daily for 30 consecutive working days. RESULTS: Among the 1571 participants, vaccination coverage for influenza in the high-risk groups was 55%, 36% for pneumococcal disease, 12% for herpes zoster (HZ), 21% for tetanus, 33% for measles, and 11% for hepatitis B. Perception of low susceptibility to disease due to good health status, concerns about side-effects and vaccines' efficacy, and mistrust in pharmaceutical companies were among common factors associated with the vaccines uptake. The strongest factor associated with the participants' vaccination status was their doctor's recommendation (odds ratio [95% confidence interval] influenza: 6.06 [4.52-8.14], pneumococcal disease: 15.73 [10.98-22.52], HZ: 17.01 [9.05-31.96], tetanus: 23.93 [16.20-35.35], measles: 33.47 [16.85-66.47], and hepatitis B: 73.92 [17.47-312.74]). Being well-informed about each vaccine was also a predictor of its uptake. CONCLUSIONS: Vaccination coverage was suboptimal and especially low in tetanus, HZ, and hepatitis B immunization. Person-centered approach, with provision of appropriate information about vaccines' safety and efficacy, responding to each patient's needs, as well as physicians' strong recommendation for vaccination are considered crucial to advocate against the spread of vaccine misinformation and increase vaccination coverage.

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.

Cell-Mediated Immune Responses After Administration of the Live or the Recombinant Zoster Vaccine: 5-Year Persistence.

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.

Recombinant Adjuvanted Zoster Vaccine and Reduced Risk of Coronavirus Disease 2019 Diagnosis and Hospitalization in Older Adults.

BACKGROUND: Some vaccines elicit nonspecific immune responses that may protect against heterologous infections. We evaluated the association between recombinant adjuvanted zoster vaccine (RZV) and coronavirus disease 2019 (COVID-19) outcomes at Kaiser Permanente Southern California. METHODS: In a cohort design, adults aged ≥50 years who received ≥1 RZV dose before 1 March 2020 were matched 1:2 to unvaccinated individuals and followed until 31 December 2020. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for COVID-19 outcomes were estimated using Cox proportional hazards regression. In a test-negative design, cases had a positive severe acute respiratory syndrome coronavirus 2 test and controls had only negative tests, during 1 March-31 December 2020. Adjusted odds ratios (aORs) and 95% CIs for RZV receipt were estimated using logistic regression. RESULTS: In the cohort design, 149 244 RZV recipients were matched to 298 488 unvaccinated individuals. The aHRs for COVID-19 diagnosis and hospitalization were 0.84 (95% CI, .81-.87) and 0.68 (95% CI, .64-.74), respectively. In the test-negative design, 8.4% of 75 726 test-positive cases and 13.1% of 340 898 test-negative controls had received ≥1 RZV dose (aOR, 0.84 [95% CI, .81-.86]). CONCLUSIONS: RZV vaccination was associated with a 16% lower risk of COVID-19 diagnosis and 32% lower risk of hospitalization. Further study of vaccine-induced nonspecific immunity for potential attenuation of future pandemics is warranted.

Association Between Immunogenicity and Reactogenicity: A Post Hoc Analysis of 2 Phase 3 Studies With the Adjuvanted Recombinant Zoster Vaccine.

A recurrent question is whether transient reactions to vaccines translate into better immune responses. Using clinical data from 2 large phase 3 studies of the recombinant zoster vaccine, we observed a small but statistically significant association between the intensity of a frequent side effect (pain) after vaccination and immune responses to vaccination. However, despite the statistical correlation, the impact on the immune response is so small, and the immune response in individuals without pain already sufficient, that pain cannot be a surrogate marker for an appropriate immune response. Reactogenicity cannot be used to predict immunity after vaccination.

The Adjuvanted Recombinant Zoster Vaccine Confers Long-Term Protection Against Herpes Zoster: Interim Results of an Extension Study of the Pivotal Phase 3 Clinical Trials ZOE-50 and ZOE-70.

BACKGROUND: This ongoing follow-up study evaluated the persistence of efficacy and immune responses for 6 additional years in adults vaccinated with the glycoprotein E (gE)-based adjuvanted recombinant zoster vaccine (RZV) at age ≥50 years in 2 pivotal efficacy trials (ZOE-50 and ZOE-70). The present interim analysis was performed after ≥2 additional years of follow-up (between 5.1 and 7.1 years [mean] post-vaccination) and includes partial data for year (Y) 8 post-vaccination. METHODS: Annual assessments were performed for efficacy against herpes zoster (HZ) from Y6 post-vaccination and for anti-gE antibody concentrations and gE-specific CD4[2+] T-cell (expressing ≥2 of 4 assessed activation markers) frequencies from Y5 post-vaccination. RESULTS: Of 7413 participants enrolled for the long-term efficacy assessment, 7277 (mean age at vaccination, 67.2 years), 813, and 108 were included in the cohorts evaluating efficacy, humoral immune responses, and cell-mediated immune responses, respectively. Efficacy of RZV against HZ through this interim analysis was 84.0% (95% confidence interval [CI], 75.9-89.8) from the start of this follow-up study and 90.9% (95% CI, 88.2-93.2) from vaccination in ZOE-50/70. Annual vaccine efficacy estimates were >84% for each year since vaccination and remained stable through this interim analysis. Anti-gE antibody geometric mean concentrations and median frequencies of gE-specific CD4[2+] T cells reached a plateau at approximately 6-fold above pre-vaccination levels. CONCLUSIONS: Efficacy against HZ and immune responses to RZV remained high, suggesting that the clinical benefit of RZV in older adults is sustained for at least 7 years post-vaccination. Clinical Trials Registration. NCT02723773.

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.