{"paper_id":"0c5c8bf5-e48d-44fa-8025-9d17e4589af4","body_text":"Real-world effectiveness of recombinant herpes zoster vaccine: A retrospective, cohort study in Japan | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Real-world effectiveness of recombinant herpes zoster vaccine: A retrospective, cohort study in Japan Satoko Ohfuji, Nozomu Toyama, Kyoko Kondo, Hisao Muto, Wakaba Fukushima This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6616279/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Aug, 2025 Read the published version in BMC Infectious Diseases → Version 1 posted 12 You are reading this latest preprint version Abstract Background: In Japan, a two-dose, recombinant herpes zoster vaccine (RZV) has been available since 2020, but vaccination coverage is low because vaccination is voluntary. This study investigated the real-world effectiveness of the RZV for preventing herpes zoster (HZ) by using clinical databases. Methods: A retrospective, cohort study was conducted by using databases created at a dermatology clinic in Miyazaki Prefecture, Japan. Vaccinated patients were extracted from the Shingrix Database, and corresponding unvaccinated patients were selected from the Outpatients Database, with individuals matched by sex, age (5-year intervals), and the outpatient visit date (±3 months from the vaccination date of the vaccinated patient). Cases of HZ as a study outcome were identified by the HZ Database until August 2024. For analysis, a conditional logistic regression model was used to calculate the odds ratio (OR) and 95% confidence interval (CI), and vaccine effectiveness was calculated as (1 - OR) × 100 (%). Results: Between 2020 and 2023, 612 patients received the RZV, and 612 corresponding unvaccinated patients were extracted from the Outpatients Database. Of them, 2 vaccinated patients (0.3%) and 13 unvaccinated patients (2%) developed HZ from the date of the vaccination/outpatient visit until August 2024 (P<0.01). The adjusted OR (95% CI) of vaccination for HZ infection was 0.16 (0.04-0.69), giving a vaccine effectiveness of 84%. Effectiveness was the same, regardless of age. Conclusion: The RZV provides high effectiveness for preventing HZ in the clinical setting. The necessity or the timing of booster vaccination warrants further investigation. Ageing society Herpes zoster Real-world setting Recombinant herpes zoster vaccine Retrospective cohort study Vaccine effectiveness. Background Herpes zoster (HZ), commonly known as shingles, is a reactivation of the varicella-zoster virus, which remains latent in the sensory ganglia after primary infection with varicella. In addition to the acute painful rash, HZ can often lead to complications such as postherpetic neuralgia and HZ ophthalmicus, which can significantly impact patients’ quality of life. The incidence of HZ and its complications increases with age, making it a significant public health concern, especially in countries with aging populations, such as Japan [ 1 – 3 ]. Moreover, the incidence of HZ has shown an upward trend in the world for a couple of decades, resulting in an increased disease burden worldwide [ 4 ]. To control HZ incidence, Shingrix, an adjuvanted recombinant herpes zoster vaccine (RZV), was developed, and it has shown high efficacy and is well tolerated, with a good safety profile in clinical trials [ 5 , 6 ]. Its efficacy against HZ reached 97% in participants aged 50 years or older [ 5 ] and 91% in participants aged 70 years or older [ 6 ]. In addition, the protective effect was sustained for up to 10 years after initial vaccination [ 7 , 8 ]. Based on these results, the RZV has been available for the prevention of HZ in Japan since 2020, along with a single-dose, live attenuated vaccine approved in 2016. However, since vaccination is voluntary, vaccination coverage is quite low, at around 10%, in Japan [ 9 ]. Several postmarketing studies confirmed RZV effectiveness of approximately 70% in the real-world setting to prevent HZ [ 10 – 13 ]. Since most of these reports involved the population in the US, further information from different populations is also important. As far as we know, no study has been reported from the Asian region. The results for RZV effectiveness in the clinical setting in Japan, where vaccination has yet to progress, may be useful for considering the need for vaccines in countries with ageing populations. The aim of the present study was to examine RZV effectiveness for the prevention of HZ by using clinical databases at a dermatology clinic in Japan. Methods Databases The present study used the following clinical databases that had already been established at a Dermatology clinic in Miyazaki Prefecture, Japan: 1) Outpatients Database; 2) Shingrix Database; and 3) HZ Database. The Outpatients Database was created for patients who visited the clinic and responded to questionnaires on awareness of HZ disease burden and its vaccine as part of routine clinical practice. The Outpatients Database has a list of 8,293 patients from February 2019 to August 2024 that contains the following information: medical record number, date of outpatient visit, age at outpatient visit, sex, and history of HZ (if any, also age at HZ diagnosis, and affected area). The Shingrix Database was created for patients who received the RZV at the clinic since 2020, and it contains the following information: medical record number, date of vaccination, age at vaccination, sex, history of HZ (if any, also age at HZ diagnosis, and affected area), and history of live attenuated HZ vaccination. The HZ Database was created for patients diagnosed with HZ at the clinic since 2014, with the following information: medical record number, month at HZ diagnosis, age at HZ diagnosis, sex, affected side, affected area, Ramsay Hunt syndrome, disseminated HZ, and hospitalization. These databases of patients up to August 2024 were linked using medical record numbers, and RZV effectiveness was examined in a retrospective, matched cohort study. Study participants The source population of this study was defined as outpatients who visited the clinic since 2020, when the RZV became available in Japan. Vaccinated patients were extracted from the Shingrix Database. Corresponding unvaccinated patients were selected from the Outpatients Database, with individuals matched 1:1 with each vaccinated patient by sex, age (5-year intervals), and the outpatient visit date (± 3 months from the date of vaccination of the vaccinated patient). To match the follow-up period to August 2024 for vaccinated and unvaccinated patients, unvaccinated patients were selected from among patients who visited the clinic on the nearest date to the date of vaccination of each vaccinated patient. Patients with a history of live attenuated HZ vaccination were excluded at the time of selection of unvaccinated patients. Selection of vaccinated or unvaccinated patients was performed independently by a researcher who did not know the patients’ outcome status. According to the Japanese Ethical Guidelines for Medical and Biological Research Involving Human Subjects, since the study used only their pre-existing data, study participants were notified about this study by displaying a poster, and patient consent for participation was obtained using an opt-out method. This protocol was approved by the Ethics Committee on Medical Research at Osaka Metropolitan University (approval no. 2024-090; approval on August 9, 2024) and was performed in accordance with the Declaration of Helsinki. Follow-up and confirmation of HZ infection The follow-up period started on the date of vaccination for vaccinated patients and the date of the outpatient visit for unvaccinated patients (baseline). The follow-up continued until the month of HZ diagnosis or to the end of the study period (August 2024). If follow-up ended at the same month as baseline, the follow-up period was regarded as 0.5 months. If a patient had a record in the HZ Database during the follow-up period, they were regarded as having a HZ diagnosis, which was the primary outcome in this study. If a patient had a record of HZ diagnosis in the HZ Database before baseline, they were considered to have a history of HZ at the time of baseline. A history of HZ was also confirmed by the information on history of HZ in the Outpatients Database or the Shingrix Database. Statistical analysis Baseline characteristics of vaccinated and unvaccinated patients were compared with chi-squared tests for categorical variables and Wilcoxon rank-sum tests for continuous variables. The incidence of HZ was compared between vaccinated and unvaccinated patients with chi-squared tests. A conditional logistic regression model was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for HZ incidence after vaccination. It was also examined with a Cox proportional hazards model considering follow-up period and is reported as the hazard ratio (HR) and 95% CI for HZ incidence after vaccination. Vaccine effectiveness (VE) was calculated as (1 - OR) × 100 (%) or (1 - HR) × 100 (%). In addition, subgroup analysis by age was performed limited to those aged 50 years or older, those aged 65 years or older, and those aged 70 years or older. Furthermore, subgroup analysis that excluded pairs with a history of live attenuated HZ vaccine was also conducted. All analyses used SAS version 9.4 software (SAS Institute, Cary, NC, USA). Results Between 2020 and 2023, 612 patients received the RZV, and the corresponding 612 unvaccinated patients were extracted from the Outpatients Database. The baseline characteristics of vaccinated and unvaccinated patients are shown in Table 1 . Age, sex, and year of vaccination or outpatient visit as matching factors were well balanced between the groups. The median age at vaccination was 71 years (range: 41–93 years). The number of patients with a history of HZ was significantly higher in the vaccinated patients (16% vs 12%, P = 0.048). In addition, there were 106 patients (17%) who had previously received a live attenuated HZ vaccine before receiving the RZV vaccine. The median follow-up period was 1.7 years in both groups. Table 1 Characteristics of patients vaccinated with the recombinant herpes zoster vaccine and unvaccinated patients. Vaccinated (N = 612) Unvaccinated (N = 612) P a Age (y) Median (range) 71 (41–93) 71 (40–88) 0.93 ≤ 49 3 (0.5%) 3 (0.5%) 1.00 50–64 126 (21%) 126 (21%) 65–74 272 (44%) 272 (44%) ≥ 75 211 (34%) 211 (34%) Sex Male 216 (35%) 216 (35%) 1.00 History of HZ Yes 98 (16%) 74 (12%) 0.048 History of live attenuated HZ vaccination Yes 106 (17%) 0 Year of baseline (vaccination or outpatient visit) 2020 8 (1%) 8 (1%) 1.00 2021 110 (18%) 110 (18%) 2022 195 (32%) 200 (32%) 2023 299 (49%) 280 (46%) 2024 0 (0%) 14 (2%) Follow-up period (y) Median (range) 1.7 (0.1–4.4) 1.7 (0.04–4.3) 0.61 HZ, herpes zoster; RZV, recombinant herpes zoster vaccine. a Calculated with chi-squared tests or Wilcoxon rank-sum tests The incidence of HZ during the follow-up period was significantly lower in vaccinated patients (0.3%) than in unvaccinated patients (2%) (Table 2 ). On univariate analysis, the OR (95% CI) of RZV vaccination for HZ incidence was 0.15 (0.04–0.68). After adjustment for history of HZ, the corresponding OR (95%CI) was 0.16 (0.04–0.69), giving a vaccine effectiveness of 84%. Subgroup analysis by age showed vaccine effectiveness of 84% for those aged 50 years or older, 91% for those aged 65 years or older, and 90% for those aged 70 years or older, all showing significant preventive effects against HZ. Table 2 Effectiveness of the recombinant herpes zoster vaccine against herpes zoster incidence: conditional logistic regression model. No. of patients HZ cases (%) Univariate OR (95%CI) Adjusted OR (95%CI) a VE Total Vaccinated 612 2 (0.3%) 0.15 (0.04–0.68) 0.16 (0.04–0.69) 84% Unvaccinated 612 13 (2%) 1.00 1.00 Subgroup by age (y) ≥ 50 Vaccinated 609 2 (0.3%) 0.15 (0.04–0.68) 0.16 (0.04–0.69) 84% Unvaccinated 609 13 (2%) 1.00 1.00 ≥ 65 Vaccinated 483 1 (0.2%) 0.09 (0.01–0.70) 0.09 (0.01–0.72) 91% Unvaccinated 483 11 (2%) 1.00 1.00 ≥ 70 Vaccinated 380 1 (0.3%) 0.10 (0.01–0.78) 0.10 (0.01–0.80) 90% Unvaccinated 380 10 (3%) 1.00 1.00 CI, confidence interval; HZ, herpes zoster; OR, odds ratio; RZV, recombinant herpes zoster vaccine; VE, vaccine effectiveness a Adjusted by history of HZ. The proportional hazards model considering follow-up period showed similar results (Supplementary Table 1). The HZ incidence rate was considerably lower for vaccinated patients (1.8 per 1000 person-years) than for unvaccinated patients (12.0 per 1000 person-years). The adjusted HR of RZV vaccination for HZ was 0.15 (0.03–0.66), giving a vaccine effectiveness of 85%. Vaccine effectiveness by age group was 85% for 50 years or older, 91% for 65 years or older, and 91% years for 70 years or older; all were significant. Even when excluding 106 patients with a history of live attenuated HZ vaccination before RZV vaccination and their corresponding paired patients, vaccine effectiveness of RZV was also observed. In the conditional logistic regression model (Table 3 ), effectiveness against HZ incidence was 92% for the total subjects, 92% for those aged 50 years or older, 91% for those aged 65 years or older, and 90% for those aged 70 years or older. The Cox proportional hazards model also confirmed the effectiveness in all subgroups (Supplementary Table 2). Table 3 The recombinant herpes zoster vaccine effectiveness among pairs without a history of live HZ vaccination. No. of patients HZ cases (%) Univariate OR (95%CI) Adjusted OR (95%CI) a VE Total Vaccinated 506 1 (0.2%) 0.08 (0.01–0.59) 0.08 (0.01–0.60) 92% Unvaccinated 506 13 (3%) 1.00 1.00 Subgroup by age (y) ≥ 50 Vaccinated 503 1 (0.2%) 0.08 (0.01–0.59) 0.08 (0.01–0.60) 92% Unvaccinated 503 13 (3%) 1.00 1.00 ≥ 65 Vaccinated 393 1 (0.3%) 0.09 (0.01–0.70) 0.09 (0.01–0.72) 91% Unvaccinated 393 11 (3%) 1.00 1.00 ≥ 70 Vaccinated 308 1 (0.3%) 0.10 (0.01–0.78) 0.10 (0.01–0.80) 90% Unvaccinated 308 10 (3%) 1.00 1.00 CI, confidence interval; HZ, herpes zoster; OR, odds ratio; RZV, recombinant herpes zoster vaccine; VE, vaccine effectiveness a Adjusted by history of HZ. The disease conditions of HZ cases in vaccinated and unvaccinated patients are shown in Table 4 . There were no cases of Ramsay Hunt syndrome or disseminated HZ in either group, and no patient required hospitalization. Table 4 Conditions of herpes zoster cases in vaccinated and unvaccinated patients HZ cases (N = 15) Vaccinated (N = 2) Unvaccinated (N = 13) Affected side Left 0 7 (54%) Right 2 (100%) 6 (46%) Both 0 0 Affected area Cervical nerve 2 (100%) 3 (23%) Lumbar nerve 0 3 (23%) Sacral nerve 0 1 (8%) Thoracic nerve 0 6 (46%) Ramsay Hunt syndrome Yes 0 0 Disseminated Yes 0 0 Hospitalization Yes 0 0 HZ, herpes zoster Discussion The present retrospective, matched cohort study showed that the RZV vaccine significantly decreased HZ incidence, with VE of 84% overall and of 91% even in those aged 70 years or older. Compared with the results of clinical trials [ 5 , 6 ], the effectiveness in the present study seemed slightly lower. The potential reason for the disparity might be the difference in outcome identification. In the clinical trials, all suspected cases of HZ were PCR-confirmed or adjudicated by an expert panel, whereas HZ identification in the present study was based on the diagnosis at the dermatology clinic. In addition, the clinical trials focused on HZ incidence from 1 month after the second dose of vaccination, considering the period with sufficient antibody induction. Although the present study compared HZ incidence since the baseline visit (i.e., the date of vaccination for vaccinated patients and the corresponding outpatient visit date for unvaccinated patients), a total of 4 patients (1 vaccinated and 3 unvaccinated) were diagnosed with HZ within the month after the baseline visit. If these 4 patients were excluded, vaccine effectiveness also reached 90% in the present study. Taken together, the more specific and strict clinical definition in the clinical trials might have resulted in higher effectiveness than in the present study. However, vaccine effectiveness in the present study might be slightly higher than in the postmarketing studies in the US [ 10 – 13 ] or the meta-analysis of combined postmarketing studies [ 14 ]. The previous postmarketing studies used health insurance data based on HZ diagnosis by ICD-10 code and prescription of antiviral medication [ 10 – 13 ], and a meta-analysis that combined the results of those studies showed vaccine effectiveness of 79% [ 14 ]. The reason for the higher effectiveness in the present study may have been the higher accuracy of HZ diagnosis and unbiased diagnosis, since one dermatologist made the HZ diagnosis in a standardized manner. This high diagnostic accuracy of HZ is verified by the 98% concordance rate between the clinical diagnosis of HZ and PCR test results for varicella-zoster virus in a previous clinical study [ 1 ]. In the present study, the incidence of HZ during the median follow-up period of 1.7 years was 0.3% for vaccinated patients and 2% for unvaccinated patients, which are comparable to the previous studies. One clinical trial that followed 7,344 vaccinated and 7,415 unvaccinated participants for an average of 3.2 years found an HZ incidence of 0.1% in vaccinated and 2.8% in unvaccinated individuals [ 5 ]. One retrospective, cohort study using the Kaiser Permanente Hawaii database showed that the incidence rate of HZ was 3.2 cases per 1000 person-years for vaccinated participants and 10.6 cases per 1000 person-years for unvaccinated participants [ 12 ]. In addition, the incidence in the present study was also similar to the previous reports of HZ risk in Japan [ 3 ]. Therefore, outcome identification in the present study seemed reliable. However, this study has the following limitations. First, since the present study used the existing databases that were created at the clinic for medical purposes, the effects of other confounding factors not included in the databases, such as comorbidities or immunosuppressive treatment, could not be evaluated. In addition, vaccine effectiveness for postherpetic neuralgia or other HZ complications could not be evaluated. In general, however, vaccine effectiveness for HZ complications such as postherpetic neuralgia or HZ ophthalmicus was expected to be higher than that against HZ incidence, as shown in the previous studies [ 11 , 12 ]. Second, there might be some misclassifications in vaccine status and outcome identification. For example, it was possible to determine whether some unvaccinated patients may have received HZ vaccination at another clinic during the follow-up period, although the possibility would be quite low. Because the doctor at the study clinic informed the outpatients regarding the disease burden of HZ and the information about HZ vaccines in detail at the time of the baseline visit, if the unvaccinated patients wished to receive vaccination, they would likely have visited the study clinic. Regarding outcome misclassification, the possibility that the patients in the present study did not visit a medical institution if they had a mild case of HZ or visited a different medical institution if they developed HZ could not be ruled out. However, we believe that misclassification of exposure and outcome status, if any, would lead to underestimation of the results and, therefore, would not affect the validity of the study results. Third, the present study could not examine the long-term effectiveness of RZV because data from 2020 to August 2024 were used, and the median follow-up period was 1.7 years (range: 0.04–4.4 years). Further studies to evaluate whether the duration of sufficient vaccine effectiveness is maintained in the real-world setting are needed, although clinical studies confirmed high effectiveness up to 10 years after initial vaccination [ 7 ]. Conclusions RZV vaccination has shown high effectiveness against HZ incidence in the real-world clinical setting. The vaccine greatly reduced the risk of HZ development, regardless of age. To address the public concern about HZ disease burden, preventive measures including vaccination should be promoted, especially in ageing societies. The necessity or the timing of booster vaccination warrants further investigation. Abbreviations CI, confidence interval; HR, hazard ratio; HZ, herpes zoster; OR, odds ratio; RZV, recombinant herpes zoster vaccine; VE, vaccine effectiveness. Declarations Ethics approval and consent to participate The study protocol was conducted in accordance with the principles of the Declaration of Helsinki, and it was approved by the Ethics Committee on Medical Research at Osaka Metropolitan University (approval no. 2024-090; approval on August 9, 2024). According to the Japanese Ethical Guidelines for Medical and Biological Research Involving Human Subjects, since the study used only their pre-existing data, study participants were notified about this study by displaying a poster, and patient consent for participation was obtained using an opt-out method. Consent for publication Not applicable. Declarations Competing Interests HM had a history of employment to GSK which is a manufacture of Shingrix. Funding This study was supported by a Grant-in-Aid for Investigation of Promotion of Health Labor Administration (Research Project for Promotion of Policies for Emerging and Re-emerging Infectious Diseases and Immunization) [Principal Investigator: Wakaba Fukushima; Grant Number: 24HA2007]. The funding body had no role in study design, data collection, data analysis, interpretation of the data, or writing of the report. Author Contribution All authors provided comments on the drafts and have read and approved the final manuscript. SO, KK and WF contributed to study design, statistical analysis, data interpretation, and manuscript writing. NT contributed to study design, data collection, data management, and data interpretation. HM contributed to conception of study design, data interpretation, and overall management. Acknowledgement The authors would like to thank the staff at the participating clinic. The authors are also grateful to Forte (www.forte-science.co.jp) for English language editing. Data Availability The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. References Toyama N, Shiraki K, Society of the Miyazaki Prefecture Dermatologists. Epidemiology of herpes zoster and its relationship to varicella in Japan: A 10-year survey of 48,388 herpes zoster cases in Miyazaki prefecture. J Med Virol. 2009;81:2053–8. Takao Y, Miyazaki Y, Okeda M, Onishi F, Yano S, Gomi Y, for the SHEZ Study Group, et al. Incidences of herpes zoster and postherpetic neuralgia in Japanese adults aged 50 years and older from a community-based prospective cohort study: The SHEZ study. J Epidemiol. 2015;25:617–25. Sato K, Adachi K, Nakamura H, Asano K, Watanabe A, Adachi R, et al. 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Recombinant zoster vaccine (Shingrix): real-world effectiveness in the first 2 years post-licensure. Clin Infect Dis. 2021;73:941–8. Sun Y, Jackson K, Dalmon CA, Shapiro BL, Nie S, Wong C, et al. Effectiveness of the recombinant zoster vaccine among Kaiser Permanente Hawaii enrollees aged 50 and older: A retrospective cohort study. Vaccine. 2021;39:3974–82. Sun Y, Kim E, Kong CL, Arnold BF, Porco TC, Acharya NR. Effectiveness of the recombinant zoster vaccine in adults aged 50 and older in the United States: a claims-based cohort study. Clin Infect Dis. 2021;73:949–56. Mbinta JF, Nguyen BP, Awuni PMA, Paynter J, Simpson CR. Post-licensure zoster vaccine effectiveness against herpes zoster and postherpetic neuralgia in older adults: a systematic review and meta-analysis. Lancet Healthy Longev. 2022;3:e263–75. Additional Declarations Competing interest reported. HM had a history of employment to GSK which is a manufacture of Shingrix. Supplementary Files SupplementaryTablesOhfuji.doc Cite Share Download PDF Status: Published Journal Publication published 05 Aug, 2025 Read the published version in BMC Infectious Diseases → Version 1 posted Editorial decision: Revision requested 30 May, 2025 Reviews received at journal 17 May, 2025 Reviews received at journal 15 May, 2025 Reviews received at journal 15 May, 2025 Reviewers agreed at journal 14 May, 2025 Reviewers agreed at journal 14 May, 2025 Reviewers agreed at journal 14 May, 2025 Reviewers agreed at journal 13 May, 2025 Reviewers invited by journal 13 May, 2025 Editor assigned by journal 09 May, 2025 Submission checks completed at journal 09 May, 2025 First submitted to journal 07 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-6616279\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":456531002,\"identity\":\"5bf024d8-db67-48fd-8583-3652382dad9f\",\"order_by\":0,\"name\":\"Satoko Ohfuji\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuklEQVRIiWNgGAWjYJACxgYGGxibjRgNzCAtaaRrOUyCo+Tbzx98OKPivJzujATGDz8Y+PIIajE4k8xsuOHMbWOzGwnMkj0MbMWEtTAks0k+bLuduO1GAoM00C+JDQQd1v8YpOUcSAvzb6K0MNwA2rKx7QBICxtxthjceGxsOONMsrHZmYdtlj0GRPhFvj/x4cOeCjs5s+PJh2/8qDhGOMSQADB6GAyOJZCiBQxqSNcyCkbBKBgFwx4AAPMFO+5I+3/eAAAAAElFTkSuQmCC\",\"orcid\":\"\",\"institution\":\"Osaka Metropolitan University Graduate School of Medicine\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Satoko\",\"middleName\":\"\",\"lastName\":\"Ohfuji\",\"suffix\":\"\"},{\"id\":456531005,\"identity\":\"0bfb7fd9-b6f2-4e11-9938-02e4bd1c50e5\",\"order_by\":1,\"name\":\"Nozomu Toyama\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Toyama Dermatologic Clinic\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Nozomu\",\"middleName\":\"\",\"lastName\":\"Toyama\",\"suffix\":\"\"},{\"id\":456531007,\"identity\":\"21117f8d-08e5-43a9-867b-db9ae60b66d4\",\"order_by\":2,\"name\":\"Kyoko Kondo\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Osaka Metropolitan University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Kyoko\",\"middleName\":\"\",\"lastName\":\"Kondo\",\"suffix\":\"\"},{\"id\":456531008,\"identity\":\"50bff873-e3c7-49ec-9336-e44daa5671d1\",\"order_by\":3,\"name\":\"Hisao Muto\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Kusuri no Aoki Co., Ltd\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Hisao\",\"middleName\":\"\",\"lastName\":\"Muto\",\"suffix\":\"\"},{\"id\":456531009,\"identity\":\"d70ca034-6d45-4f9b-8a9e-ec4bf40c3c81\",\"order_by\":4,\"name\":\"Wakaba Fukushima\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Osaka Metropolitan University Graduate School of Medicine\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Wakaba\",\"middleName\":\"\",\"lastName\":\"Fukushima\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2025-05-08 03:38:15\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-6616279/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-6616279/v1\",\"draftVersion\":[],\"editorialEvents\":[{\"content\":\"https://doi.org/10.1186/s12879-025-11369-5\",\"type\":\"published\",\"date\":\"2025-08-05T15:57:21+00:00\"}],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":88814127,\"identity\":\"33627f8e-4e0a-4709-a23a-9d26ccf6c87d\",\"added_by\":\"auto\",\"created_at\":\"2025-08-11 16:07:20\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":659235,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6616279/v1/39284808-da79-458b-b6a2-d0f77716c0a6.pdf\"},{\"id\":82817268,\"identity\":\"7301382f-fcf3-4f12-86d8-119f92425465\",\"added_by\":\"auto\",\"created_at\":\"2025-05-15 14:31:38\",\"extension\":\"doc\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":79872,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"SupplementaryTablesOhfuji.doc\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6616279/v1/91c0ffbd290ca35ff9c79436.doc\"}],\"financialInterests\":\"Competing interest reported. HM had a history of employment to GSK which is a manufacture of Shingrix.\",\"formattedTitle\":\"Real-world effectiveness of recombinant herpes zoster vaccine: A retrospective, cohort study in Japan\",\"fulltext\":[{\"header\":\"Background\",\"content\":\"\\u003cp\\u003eHerpes zoster (HZ), commonly known as shingles, is a reactivation of the varicella-zoster virus, which remains latent in the sensory ganglia after primary infection with varicella. In addition to the acute painful rash, HZ can often lead to complications such as postherpetic neuralgia and HZ ophthalmicus, which can significantly impact patients\\u0026rsquo; quality of life. The incidence of HZ and its complications increases with age, making it a significant public health concern, especially in countries with aging populations, such as Japan [\\u003cspan additionalcitationids=\\\"CR2\\\" citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]. Moreover, the incidence of HZ has shown an upward trend in the world for a couple of decades, resulting in an increased disease burden worldwide [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eTo control HZ incidence, Shingrix, an adjuvanted recombinant herpes zoster vaccine (RZV), was developed, and it has shown high efficacy and is well tolerated, with a good safety profile in clinical trials [\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e]. Its efficacy against HZ reached 97% in participants aged 50 years or older [\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e] and 91% in participants aged 70 years or older [\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e]. In addition, the protective effect was sustained for up to 10 years after initial vaccination [\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e]. Based on these results, the RZV has been available for the prevention of HZ in Japan since 2020, along with a single-dose, live attenuated vaccine approved in 2016. However, since vaccination is voluntary, vaccination coverage is quite low, at around 10%, in Japan [\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eSeveral postmarketing studies confirmed RZV effectiveness of approximately 70% in the real-world setting to prevent HZ [\\u003cspan additionalcitationids=\\\"CR11 CR12\\\" citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e]. Since most of these reports involved the population in the US, further information from different populations is also important. As far as we know, no study has been reported from the Asian region. The results for RZV effectiveness in the clinical setting in Japan, where vaccination has yet to progress, may be useful for considering the need for vaccines in countries with ageing populations. The aim of the present study was to examine RZV effectiveness for the prevention of HZ by using clinical databases at a dermatology clinic in Japan.\\u003c/p\\u003e\"},{\"header\":\"Methods\",\"content\":\"\\u003cp\\u003eDatabases\\u003c/p\\u003e \\u003cp\\u003eThe present study used the following clinical databases that had already been established at a Dermatology clinic in Miyazaki Prefecture, Japan: 1) Outpatients Database; 2) Shingrix Database; and 3) HZ Database.\\u003c/p\\u003e \\u003cp\\u003eThe Outpatients Database was created for patients who visited the clinic and responded to questionnaires on awareness of HZ disease burden and its vaccine as part of routine clinical practice. The Outpatients Database has a list of 8,293 patients from February 2019 to August 2024 that contains the following information: medical record number, date of outpatient visit, age at outpatient visit, sex, and history of HZ (if any, also age at HZ diagnosis, and affected area).\\u003c/p\\u003e \\u003cp\\u003eThe Shingrix Database was created for patients who received the RZV at the clinic since 2020, and it contains the following information: medical record number, date of vaccination, age at vaccination, sex, history of HZ (if any, also age at HZ diagnosis, and affected area), and history of live attenuated HZ vaccination.\\u003c/p\\u003e \\u003cp\\u003eThe HZ Database was created for patients diagnosed with HZ at the clinic since 2014, with the following information: medical record number, month at HZ diagnosis, age at HZ diagnosis, sex, affected side, affected area, Ramsay Hunt syndrome, disseminated HZ, and hospitalization.\\u003c/p\\u003e \\u003cp\\u003eThese databases of patients up to August 2024 were linked using medical record numbers, and RZV effectiveness was examined in a retrospective, matched cohort study.\\u003c/p\\u003e \\u003cp\\u003eStudy participants\\u003c/p\\u003e \\u003cp\\u003eThe source population of this study was defined as outpatients who visited the clinic since 2020, when the RZV became available in Japan. Vaccinated patients were extracted from the Shingrix Database. Corresponding unvaccinated patients were selected from the Outpatients Database, with individuals matched 1:1 with each vaccinated patient by sex, age (5-year intervals), and the outpatient visit date (\\u0026plusmn;\\u0026thinsp;3 months from the date of vaccination of the vaccinated patient). To match the follow-up period to August 2024 for vaccinated and unvaccinated patients, unvaccinated patients were selected from among patients who visited the clinic on the nearest date to the date of vaccination of each vaccinated patient. Patients with a history of live attenuated HZ vaccination were excluded at the time of selection of unvaccinated patients. Selection of vaccinated or unvaccinated patients was performed independently by a researcher who did not know the patients\\u0026rsquo; outcome status.\\u003c/p\\u003e \\u003cp\\u003e According to the Japanese Ethical Guidelines for Medical and Biological Research Involving Human Subjects, since the study used only their pre-existing data, study participants were notified about this study by displaying a poster, and patient consent for participation was obtained using an opt-out method. This protocol was approved by the Ethics Committee on Medical Research at Osaka Metropolitan University (approval no. 2024-090; approval on August 9, 2024) and was performed in accordance with the Declaration of Helsinki.\\u003c/p\\u003e \\u003cp\\u003eFollow-up and confirmation of HZ infection\\u003c/p\\u003e \\u003cp\\u003eThe follow-up period started on the date of vaccination for vaccinated patients and the date of the outpatient visit for unvaccinated patients (baseline). The follow-up continued until the month of HZ diagnosis or to the end of the study period (August 2024). If follow-up ended at the same month as baseline, the follow-up period was regarded as 0.5 months.\\u003c/p\\u003e \\u003cp\\u003eIf a patient had a record in the HZ Database during the follow-up period, they were regarded as having a HZ diagnosis, which was the primary outcome in this study. If a patient had a record of HZ diagnosis in the HZ Database before baseline, they were considered to have a history of HZ at the time of baseline. A history of HZ was also confirmed by the information on history of HZ in the Outpatients Database or the Shingrix Database.\\u003c/p\\u003e \\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStatistical analysis\\u003c/h2\\u003e \\u003cp\\u003eBaseline characteristics of vaccinated and unvaccinated patients were compared with chi-squared tests for categorical variables and Wilcoxon rank-sum tests for continuous variables.\\u003c/p\\u003e \\u003cp\\u003eThe incidence of HZ was compared between vaccinated and unvaccinated patients with chi-squared tests. A conditional logistic regression model was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for HZ incidence after vaccination. It was also examined with a Cox proportional hazards model considering follow-up period and is reported as the hazard ratio (HR) and 95% CI for HZ incidence after vaccination. Vaccine effectiveness (VE) was calculated as (1 - OR) \\u0026times; 100 (%) or (1 - HR) \\u0026times; 100 (%).\\u003c/p\\u003e \\u003cp\\u003eIn addition, subgroup analysis by age was performed limited to those aged 50 years or older, those aged 65 years or older, and those aged 70 years or older. Furthermore, subgroup analysis that excluded pairs with a history of live attenuated HZ vaccine was also conducted. All analyses used SAS version 9.4 software (SAS Institute, Cary, NC, USA).\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cp\\u003eBetween 2020 and 2023, 612 patients received the RZV, and the corresponding 612 unvaccinated patients were extracted from the Outpatients Database. The baseline characteristics of vaccinated and unvaccinated patients are shown in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e. Age, sex, and year of vaccination or outpatient visit as matching factors were well balanced between the groups. The median age at vaccination was 71 years (range: 41\\u0026ndash;93 years). The number of patients with a history of HZ was significantly higher in the vaccinated patients (16% vs 12%, P\\u0026thinsp;=\\u0026thinsp;0.048). In addition, there were 106 patients (17%) who had previously received a live attenuated HZ vaccine before receiving the RZV vaccine. The median follow-up period was 1.7 years in both groups.\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eCharacteristics of patients vaccinated with the recombinant herpes zoster vaccine and unvaccinated patients.\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"5\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eVaccinated\\u003c/p\\u003e \\u003cp\\u003e(N\\u0026thinsp;=\\u0026thinsp;612)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eUnvaccinated\\u003c/p\\u003e \\u003cp\\u003e(N\\u0026thinsp;=\\u0026thinsp;612)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eP \\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAge (y)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eMedian (range)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e71 (41\\u0026ndash;93)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e71 (40\\u0026ndash;88)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.93\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e\\u0026le;\\u0026thinsp;49\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e3 (0.5%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e3 (0.5%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e50\\u0026ndash;64\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e126 (21%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e126 (21%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e65\\u0026ndash;74\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e272 (44%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e272 (44%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e\\u0026ge;\\u0026thinsp;75\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e211 (34%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e211 (34%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSex\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eMale\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e216 (35%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e216 (35%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eHistory of HZ\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eYes\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e98 (16%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e74 (12%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.048\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eHistory of live attenuated HZ vaccination\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eYes\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e106 (17%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eYear of baseline (vaccination or outpatient visit)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e2020\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e8 (1%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e8 (1%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e2021\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e110 (18%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e110 (18%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e2022\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e195 (32%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e200 (32%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e2023\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e299 (49%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e280 (46%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e2024\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0 (0%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e14 (2%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eFollow-up period (y)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eMedian (range)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.7 (0.1\\u0026ndash;4.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1.7 (0.04\\u0026ndash;4.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.61\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"5\\\"\\u003eHZ, herpes zoster; RZV, recombinant herpes zoster vaccine.\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"5\\\"\\u003e\\u003csup\\u003ea\\u003c/sup\\u003e Calculated with chi-squared tests or Wilcoxon rank-sum tests\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eThe incidence of HZ during the follow-up period was significantly lower in vaccinated patients (0.3%) than in unvaccinated patients (2%) (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e). On univariate analysis, the OR (95% CI) of RZV vaccination for HZ incidence was 0.15 (0.04\\u0026ndash;0.68). After adjustment for history of HZ, the corresponding OR (95%CI) was 0.16 (0.04\\u0026ndash;0.69), giving a vaccine effectiveness of 84%. Subgroup analysis by age showed vaccine effectiveness of 84% for those aged 50 years or older, 91% for those aged 65 years or older, and 90% for those aged 70 years or older, all showing significant preventive effects against HZ.\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab2\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 2\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eEffectiveness of the recombinant herpes zoster vaccine against herpes zoster incidence: conditional logistic regression model.\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"7\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c6\\\" colnum=\\\"6\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c7\\\" colnum=\\\"7\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eNo. of patients\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eHZ cases (%)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eUnivariate\\u003c/p\\u003e \\u003cp\\u003eOR (95%CI)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003eAdjusted\\u003c/p\\u003e \\u003cp\\u003eOR (95%CI) \\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003eVE\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eTotal\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eVaccinated\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e612\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e2 (0.3%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.15 (0.04\\u0026ndash;0.68)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.16 (0.04\\u0026ndash;0.69)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e84%\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eUnvaccinated\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e612\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e13 (2%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSubgroup by age (y)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026ge;\\u0026thinsp;50\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eVaccinated\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e609\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e2 (0.3%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.15 (0.04\\u0026ndash;0.68)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.16 (0.04\\u0026ndash;0.69)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e84%\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eUnvaccinated\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e609\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e13 (2%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026ge;\\u0026thinsp;65\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eVaccinated\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e483\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1 (0.2%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.09 (0.01\\u0026ndash;0.70)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.09 (0.01\\u0026ndash;0.72)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e91%\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eUnvaccinated\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e483\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e11 (2%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026ge;\\u0026thinsp;70\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eVaccinated\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e380\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1 (0.3%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.10 (0.01\\u0026ndash;0.78)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.10 (0.01\\u0026ndash;0.80)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e90%\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eUnvaccinated\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e380\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e10 (3%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"7\\\"\\u003eCI, confidence interval; HZ, herpes zoster; OR, odds ratio; RZV, recombinant herpes zoster vaccine; VE, vaccine effectiveness\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"7\\\"\\u003e\\u003csup\\u003ea\\u003c/sup\\u003e Adjusted by history of HZ.\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eThe proportional hazards model considering follow-up period showed similar results (Supplementary Table\\u0026nbsp;1). The HZ incidence rate was considerably lower for vaccinated patients (1.8 per 1000 person-years) than for unvaccinated patients (12.0 per 1000 person-years). The adjusted HR of RZV vaccination for HZ was 0.15 (0.03\\u0026ndash;0.66), giving a vaccine effectiveness of 85%. Vaccine effectiveness by age group was 85% for 50 years or older, 91% for 65 years or older, and 91% years for 70 years or older; all were significant.\\u003c/p\\u003e \\u003cp\\u003eEven when excluding 106 patients with a history of live attenuated HZ vaccination before RZV vaccination and their corresponding paired patients, vaccine effectiveness of RZV was also observed. In the conditional logistic regression model (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e), effectiveness against HZ incidence was 92% for the total subjects, 92% for those aged 50 years or older, 91% for those aged 65 years or older, and 90% for those aged 70 years or older. The Cox proportional hazards model also confirmed the effectiveness in all subgroups (Supplementary Table\\u0026nbsp;2).\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab3\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 3\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eThe recombinant herpes zoster vaccine effectiveness among pairs without a history of live HZ vaccination.\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"7\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c6\\\" colnum=\\\"6\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c7\\\" colnum=\\\"7\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eNo. of patients\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eHZ cases (%)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eUnivariate\\u003c/p\\u003e \\u003cp\\u003eOR (95%CI)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003eAdjusted\\u003c/p\\u003e \\u003cp\\u003eOR (95%CI) \\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003eVE\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eTotal\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eVaccinated\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e506\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1 (0.2%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.08 (0.01\\u0026ndash;0.59)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.08 (0.01\\u0026ndash;0.60)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e92%\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eUnvaccinated\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e506\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e13 (3%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSubgroup by age (y)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026ge;\\u0026thinsp;50\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eVaccinated\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e503\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1 (0.2%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.08 (0.01\\u0026ndash;0.59)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.08 (0.01\\u0026ndash;0.60)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e92%\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eUnvaccinated\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e503\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e13 (3%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026ge;\\u0026thinsp;65\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eVaccinated\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e393\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1 (0.3%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.09 (0.01\\u0026ndash;0.70)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.09 (0.01\\u0026ndash;0.72)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e91%\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eUnvaccinated\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e393\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e11 (3%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026ge;\\u0026thinsp;70\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eVaccinated\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e308\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1 (0.3%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.10 (0.01\\u0026ndash;0.78)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.10 (0.01\\u0026ndash;0.80)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e90%\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eUnvaccinated\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e308\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e10 (3%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"7\\\"\\u003eCI, confidence interval; HZ, herpes zoster; OR, odds ratio; RZV, recombinant herpes zoster vaccine; VE, vaccine effectiveness\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"7\\\"\\u003e\\u003csup\\u003ea\\u003c/sup\\u003e Adjusted by history of HZ.\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eThe disease conditions of HZ cases in vaccinated and unvaccinated patients are shown in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e. There were no cases of Ramsay Hunt syndrome or disseminated HZ in either group, and no patient required hospitalization.\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab4\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 4\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eConditions of herpes zoster cases in vaccinated and unvaccinated patients\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"4\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eHZ cases (N\\u0026thinsp;=\\u0026thinsp;15)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eVaccinated (N\\u0026thinsp;=\\u0026thinsp;2)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eUnvaccinated (N\\u0026thinsp;=\\u0026thinsp;13)\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAffected side\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eLeft\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e7 (54%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eRight\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2 (100%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e6 (46%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eBoth\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAffected area\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eCervical nerve\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2 (100%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e3 (23%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eLumbar nerve\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e3 (23%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eSacral nerve\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1 (8%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eThoracic nerve\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e6 (46%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eRamsay Hunt syndrome\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eYes\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eDisseminated\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eYes\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eHospitalization\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eYes\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"4\\\"\\u003eHZ, herpes zoster\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eThe present retrospective, matched cohort study showed that the RZV vaccine significantly decreased HZ incidence, with VE of 84% overall and of 91% even in those aged 70 years or older.\\u003c/p\\u003e \\u003cp\\u003eCompared with the results of clinical trials [\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e], the effectiveness in the present study seemed slightly lower. The potential reason for the disparity might be the difference in outcome identification. In the clinical trials, all suspected cases of HZ were PCR-confirmed or adjudicated by an expert panel, whereas HZ identification in the present study was based on the diagnosis at the dermatology clinic. In addition, the clinical trials focused on HZ incidence from 1 month after the second dose of vaccination, considering the period with sufficient antibody induction. Although the present study compared HZ incidence since the baseline visit (i.e., the date of vaccination for vaccinated patients and the corresponding outpatient visit date for unvaccinated patients), a total of 4 patients (1 vaccinated and 3 unvaccinated) were diagnosed with HZ within the month after the baseline visit. If these 4 patients were excluded, vaccine effectiveness also reached 90% in the present study. Taken together, the more specific and strict clinical definition in the clinical trials might have resulted in higher effectiveness than in the present study.\\u003c/p\\u003e \\u003cp\\u003eHowever, vaccine effectiveness in the present study might be slightly higher than in the postmarketing studies in the US [\\u003cspan additionalcitationids=\\\"CR11 CR12\\\" citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e] or the meta-analysis of combined postmarketing studies [\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e]. The previous postmarketing studies used health insurance data based on HZ diagnosis by ICD-10 code and prescription of antiviral medication [\\u003cspan additionalcitationids=\\\"CR11 CR12\\\" citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e], and a meta-analysis that combined the results of those studies showed vaccine effectiveness of 79% [\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e]. The reason for the higher effectiveness in the present study may have been the higher accuracy of HZ diagnosis and unbiased diagnosis, since one dermatologist made the HZ diagnosis in a standardized manner. This high diagnostic accuracy of HZ is verified by the 98% concordance rate between the clinical diagnosis of HZ and PCR test results for varicella-zoster virus in a previous clinical study [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eIn the present study, the incidence of HZ during the median follow-up period of 1.7 years was 0.3% for vaccinated patients and 2% for unvaccinated patients, which are comparable to the previous studies. One clinical trial that followed 7,344 vaccinated and 7,415 unvaccinated participants for an average of 3.2 years found an HZ incidence of 0.1% in vaccinated and 2.8% in unvaccinated individuals [\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e]. One retrospective, cohort study using the Kaiser Permanente Hawaii database showed that the incidence rate of HZ was 3.2 cases per 1000 person-years for vaccinated participants and 10.6 cases per 1000 person-years for unvaccinated participants [\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e]. In addition, the incidence in the present study was also similar to the previous reports of HZ risk in Japan [\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]. Therefore, outcome identification in the present study seemed reliable.\\u003c/p\\u003e \\u003cp\\u003eHowever, this study has the following limitations. First, since the present study used the existing databases that were created at the clinic for medical purposes, the effects of other confounding factors not included in the databases, such as comorbidities or immunosuppressive treatment, could not be evaluated. In addition, vaccine effectiveness for postherpetic neuralgia or other HZ complications could not be evaluated. In general, however, vaccine effectiveness for HZ complications such as postherpetic neuralgia or HZ ophthalmicus was expected to be higher than that against HZ incidence, as shown in the previous studies [\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e]. Second, there might be some misclassifications in vaccine status and outcome identification. For example, it was possible to determine whether some unvaccinated patients may have received HZ vaccination at another clinic during the follow-up period, although the possibility would be quite low. Because the doctor at the study clinic informed the outpatients regarding the disease burden of HZ and the information about HZ vaccines in detail at the time of the baseline visit, if the unvaccinated patients wished to receive vaccination, they would likely have visited the study clinic. Regarding outcome misclassification, the possibility that the patients in the present study did not visit a medical institution if they had a mild case of HZ or visited a different medical institution if they developed HZ could not be ruled out. However, we believe that misclassification of exposure and outcome status, if any, would lead to underestimation of the results and, therefore, would not affect the validity of the study results. Third, the present study could not examine the long-term effectiveness of RZV because data from 2020 to August 2024 were used, and the median follow-up period was 1.7 years (range: 0.04\\u0026ndash;4.4 years). Further studies to evaluate whether the duration of sufficient vaccine effectiveness is maintained in the real-world setting are needed, although clinical studies confirmed high effectiveness up to 10 years after initial vaccination [\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e].\\u003c/p\\u003e\"},{\"header\":\"Conclusions\",\"content\":\"\\u003cp\\u003eRZV vaccination has shown high effectiveness against HZ incidence in the real-world clinical setting. The vaccine greatly reduced the risk of HZ development, regardless of age. To address the public concern about HZ disease burden, preventive measures including vaccination should be promoted, especially in ageing societies. The necessity or the timing of booster vaccination warrants further investigation.\\u003c/p\\u003e\"},{\"header\":\"Abbreviations\",\"content\":\"\\u003cp\\u003eCI, confidence interval; HR, hazard ratio; HZ, herpes zoster; OR, odds ratio; RZV, recombinant herpes zoster vaccine; VE, vaccine effectiveness.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\" \\u003cp\\u003e \\u003cstrong\\u003eEthics approval and consent to participate\\u003c/strong\\u003e \\u003c/p\\u003e\\u003cp\\u003e The study protocol was conducted in accordance with the principles of the Declaration of Helsinki, and it was approved by the Ethics Committee on Medical Research at Osaka Metropolitan University (approval no. 2024-090; approval on August 9, 2024). According to the Japanese Ethical Guidelines for Medical and Biological Research Involving Human Subjects, since the study used only their pre-existing data, study participants were notified about this study by displaying a poster, and patient consent for participation was obtained using an opt-out method.\\u003c/p\\u003e \\u003cp\\u003e\\u003c/p\\u003e \\u003cp\\u003e \\u003cstrong\\u003eConsent for publication\\u003c/strong\\u003e \\u003c/p\\u003e\\u003cp\\u003eNot applicable.\\u003c/p\\u003e \\u003cp\\u003e\\u003c/p\\u003e\\u003ch2\\u003eDeclarations\\u003c/h2\\u003e\\u003cp\\u003e\\u003cstrong\\u003eCompeting Interests\\u003c/strong\\u003e\\u003c/p\\u003e\\u003cp\\u003eHM had a history of employment to GSK which is a manufacture of Shingrix.\\u003c/p\\u003e\\u003cp\\u003e\\u003c/p\\u003e\\u003ch2\\u003eFunding\\u003c/h2\\u003e \\u003cp\\u003eThis study was supported by a Grant-in-Aid for Investigation of Promotion of Health Labor Administration (Research Project for Promotion of Policies for Emerging and Re-emerging Infectious Diseases and Immunization) [Principal Investigator: Wakaba Fukushima; Grant Number: 24HA2007]. The funding body had no role in study design, data collection, data analysis, interpretation of the data, or writing of the report.\\u003c/p\\u003e\\u003ch2\\u003eAuthor Contribution\\u003c/h2\\u003e\\u003cp\\u003eAll authors provided comments on the drafts and have read and approved the final manuscript. SO, KK and WF contributed to study design, statistical analysis, data interpretation, and manuscript writing. NT contributed to study design, data collection, data management, and data interpretation. HM contributed to conception of study design, data interpretation, and overall management.\\u003c/p\\u003e\\u003ch2\\u003eAcknowledgement\\u003c/h2\\u003e\\u003cp\\u003eThe authors would like to thank the staff at the participating clinic. The authors are also grateful to Forte (www.forte-science.co.jp) for English language editing.\\u003c/p\\u003e\\u003ch2\\u003eData Availability\\u003c/h2\\u003e\\u003cp\\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eToyama N, Shiraki K, Society of the Miyazaki Prefecture Dermatologists. Epidemiology of herpes zoster and its relationship to varicella in Japan: A 10-year survey of 48,388 herpes zoster cases in Miyazaki prefecture. J Med Virol. 2009;81:2053\\u0026ndash;8.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eTakao Y, Miyazaki Y, Okeda M, Onishi F, Yano S, Gomi Y, for the SHEZ Study Group, et al. Incidences of herpes zoster and postherpetic neuralgia in Japanese adults aged 50 years and older from a community-based prospective cohort study: The SHEZ study. J Epidemiol. 2015;25:617\\u0026ndash;25.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSato K, Adachi K, Nakamura H, Asano K, Watanabe A, Adachi R, et al. Burden of herpes zoster and postherpetic neuralgia in Japanese adults 60 years of age or older: Results from an observational, prospective, physician practice-based cohort study. J Dermatol. 2017;44:414\\u0026ndash;22.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eJiang Y, Luo Y, Xiao X, Li X, Hu Y, Liu C, et al. Global, regional, and national burdens of vaccine-preventable infectious diseases with high incidence among middle-aged and older adults aged 55\\u0026ndash;89 years from 1990 to 2021: Results from the global burden of disease study 2021. Vaccine. 2025;49:126786.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eLal H, Cunningham AL, Godeaux O, Chlibek R, Diez-Domingo J, Hwang SJ, ZOE-50 Study Group, et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med. 2015;372:2087\\u0026ndash;96.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eCunningham AL, Lal H, Kovac M, Chlibek R, Hwang SJ, D\\u0026iacute;ez-Domingo J, ZOE-70 Study Group, et al. Efficacy of the herpes zoster subunit vaccine in adults 70 years of age or older. N Engl J Med. 2016;375:1019\\u0026ndash;32.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eStrezova A, Diez-Domingo J, Al Shawafi K, Tinoco JC, Shi M, Pirrotta P, et al. Zoster-049 Study Group. Long-term protection against herpes zoster by the adjuvanted recombinant zoster vaccine: interim efficacy, immunogenicity, and safety results up to 10 years after initial vaccination. Open Forum Infect Dis. 2022;9:ofac485.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBoutry C, Hastie A, Diez-Domingo J, Tinoco JC, Yu CJ, Andrews C, et al. Zoster-049 Study Group. 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. Clin Infect Dis. 2022;74:1459\\u0026ndash;67.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMachida M, Fukushima S, Saitoh A, Inoue S, Tabuchi T. Uptake among four indicated vaccines by adults aged 65 years and older in Japan, 2023. Vaccine. 2024;42:125985.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eZerbo O, Bartlett J, Fireman B, Lewis N, Goddard K, Dooling K, et al. Effectiveness of recombinant zoster vaccine against herpes zoster in a real-world setting. Ann Intern Med. 2024;177:189\\u0026ndash;95.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eIzurieta HS, Wu X, Forshee R, Lu Y, Sung HM, Agger PE, et al. Recombinant zoster vaccine (Shingrix): real-world effectiveness in the first 2 years post-licensure. Clin Infect Dis. 2021;73:941\\u0026ndash;8.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSun Y, Jackson K, Dalmon CA, Shapiro BL, Nie S, Wong C, et al. Effectiveness of the recombinant zoster vaccine among Kaiser Permanente Hawaii enrollees aged 50 and older: A retrospective cohort study. Vaccine. 2021;39:3974\\u0026ndash;82.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSun Y, Kim E, Kong CL, Arnold BF, Porco TC, Acharya NR. Effectiveness of the recombinant zoster vaccine in adults aged 50 and older in the United States: a claims-based cohort study. Clin Infect Dis. 2021;73:949\\u0026ndash;56.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMbinta JF, Nguyen BP, Awuni PMA, Paynter J, Simpson CR. Post-licensure zoster vaccine effectiveness against herpes zoster and postherpetic neuralgia in older adults: a systematic review and meta-analysis. Lancet Healthy Longev. 2022;3:e263\\u0026ndash;75.\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":true,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"bmc-infectious-diseases\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"infd\",\"sideBox\":\"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)\",\"snPcode\":\"\",\"submissionUrl\":\"https://www.editorialmanager.com/infd\",\"title\":\"BMC Infectious Diseases\",\"twitterHandle\":\"#bmcinfectdis\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Ageing society, Herpes zoster, Real-world setting, Recombinant herpes zoster vaccine, Retrospective cohort study, Vaccine effectiveness.\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-6616279/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-6616279/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground:\\u003c/strong\\u003eIn Japan, a two-dose, recombinant herpes zoster vaccine (RZV) has been available since 2020, but vaccination coverage is low because vaccination is voluntary. This study investigated the real-world effectiveness of the RZV for preventing herpes zoster (HZ) by using clinical databases.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMethods: \\u003c/strong\\u003eA retrospective, cohort study was conducted by using databases created at a dermatology clinic in Miyazaki Prefecture, Japan. Vaccinated patients were extracted from the Shingrix Database, and corresponding unvaccinated patients were selected from the Outpatients Database, with individuals matched by sex, age (5-year intervals), and the outpatient visit date (±3 months from the vaccination date of the vaccinated patient). Cases of HZ as a study outcome were identified by the HZ Database until August 2024. For analysis, a conditional logistic regression model was used to calculate the odds ratio (OR) and 95% confidence interval (CI), and vaccine effectiveness was calculated as (1 - OR) × 100 (%).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eResults: \\u003c/strong\\u003eBetween 2020 and 2023, 612 patients received the RZV, and 612 corresponding unvaccinated patients were extracted from the Outpatients Database. Of them, 2 vaccinated patients (0.3%) and 13 unvaccinated patients (2%) developed HZ from the date of the vaccination/outpatient visit until August 2024 (P\\u0026lt;0.01). The adjusted OR (95% CI) of vaccination for HZ infection was 0.16 (0.04-0.69), giving a vaccine effectiveness of 84%. Effectiveness was the same, regardless of age.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusion: \\u003c/strong\\u003eThe RZV provides high effectiveness for preventing HZ in the clinical setting. 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