Immunogenicity and safety of the domestic and imported live-attenuated varicella vaccine in healthy Chinese population: A systematic review and meta-analysis

Immunogenicity and safety of the domestic and imported live-attenuated varicella vaccine in healthy Chinese population: A systematic review and meta-analysis | 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 Systematic Review Immunogenicity and safety of the domestic and imported live-attenuated varicella vaccine in healthy Chinese population: A systematic review and meta-analysis Yemin Yuan, Tong Wang, Yiqi Xia, Zhenyu Shi, Ping He This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5061401/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objectives This study aimed to synthesize the available evidence to compare the immunogenicity and safety of domestic and imported live-attenuated varicella vaccine (VarV) in healthy Chinese population. Methods PubMed, Web of Science, Embase, China National Knowledge Internet (CNKI), Wan Fang Database, and Chinese Biomedical Literature Service System (SinoMed) were searched using predefined search terms to identify relevant studies. The included articles reported varicella vaccine administration in healthy Chinese population. We calculated the pooled proportion of seroconversions and adverse events, and assessed the quality of each study using the modified Jadad Scale and Newcastle Ottawa Scale (NOS). Results The pooled seroconversion proportion of domestic Varv was 89% (95%CI: 86%-91%) and that of imported Varv was 93% (95%CI: 88%-98%). The difference was not statistically significant. The pooled proportion of systemic reactions for domestic Varv (11%, 95%CI: 10%-13%) was higher than that of imported Varv (8%, 95%CI: 6%-10%; χ 2 = 8.04, P < 0.001), but the results were opposite for local reactions (domestic Varv: 3%, 95%CI: 2%-3%; imported Varv: 7%, 95%CI: 3%-10%; χ 2 = 5.30, P = 0.020). Conclusions Both domestic and imported varicella vaccines are effective and safe in the Chinese population. More evidence on imported vaccines is needed in the future to supplement our findings. Varicella vaccine Immunogenicity Safety China Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Varicella (chickenpox) is an infectious disease caused by the varicella zoster virus (VZV) affecting children, adolescents, and adults [ 1 ]. Varicella is very contagious through its transmission by direct contact with vesicular skin lesions that contain high titers of infectious virus and respiratory droplets, which is prevalent globally and has a substantial disease burden [ 2 ]. The annual global burden of varicella was estimated to be around 140 million cases with 4.2 million severe complications requiring hospitalisation, and 4,200 deaths [ 3 ]. Primary healthcare visits for varicella accounted for 30%-85% of total direct costs; hospitalization costs ranged from $ 1,308 to $ 38,268 per episode, contributing between 2% and 60% to total direct costs [ 4 ]. Recently, the incidence of varicella has increased significantly in China. The reported incidence of varicella increased from 3.17/100,000 (41,211 cases) to 70.14/100,000 (979,482 cases) during the period 2005–2019 [ 5 , 6 ]. A total of 10,446 varicella public health emergency events were reported in China from 2007 to 2021, with 261 (in 2012) to 1,327 (in 2018) reported annually [ 7 ]. Vaccination is the most effective approach against varicella. In the United States and Japan, since the implementation of varicella vaccination program, the incidence of varicella has decreased substantially [ 8 ], as has the hospitalization and mortality rate [ 9 , 10 ]. Currently, varicella vaccine has not been included in national immunization programmes in China [ 11 ]. The average chickenpox vaccination rate in China was 61.1% (95%CI: 55.7%-66.5%) [ 12 ], which was significantly lower than that in Spain, Italy, Germany and other countries that included chickenpox vaccine in national or regional immunization programmes [ 13 , 14 ]. Moreover, the positive rate of VZV IgG antibody in healthy population in China was low (64%, 95%CI: 60%-67%) [ 15 ]. Worldwide, there are several formulations of varicella vaccines; all contain live attenuated VZV, and all, except the vaccine licensed in South Korea, are based on the Oka strain of VZV isolated in Japan [ 16 ]. Imported live-attenuated varicella vaccine (VarV) began to be introduced into China in 1997, and after 2001, a number of domestic VarV was also developed and made available. In the application of VarV, managers, doctors, vaccine recipients, and parents have concerns about the safety and immunogenicity of domestic VarV. Additionally, the cost of imported varicella vaccine is often higher than domestic options, which can limit the widespread adoption and promotion of varicella vaccination in China. Therefore, this study used systematic review and meta-analysis to comprehensively analyze the published data of domestic Varv and imported VarV in Chinese population in recent years. This study aimed to compare the immunogenicity and safety of domestic Varv and imported VarV, and to provide reference for the further application of VarV in Chinese population. Methods We performed a systematic review and meta-analysis using PRISMA guidelines [ 17 ]. The protocol was registered on PROSPERO ( www.crd.york.ac.uk/prospero/ ; identifier CRD42024546352). Search strategy We searched PubMed, Web of Science, Embase, China National Knowledge Internet (CNKI), Wan Fang Database, Chinese Biomedical Literature Service System (SinoMed) databases for articles until March 15, 2024 in any language. The following terms were used in different combinations and constructions depending on the applied database. We used search terms including “varicella zoster virus infection”, “varicella”, “chickenpox”, “immunization”, “vaccination”, “ chickenpox vaccine”, “vaccines”, “vaccine”, “safety”, “security”, “adverse effect”, “adverse reaction”, “side effect”, “side-effect”, “side reaction”, “immunogenicity”, “efficacy”, “potency”, “effectiveness”, and “effect”. “China” or “Chinese” were used when searching for English articles to identify articles that presented data on immunogenicity and safety in Chinese population. Details of the complete search strategy are available in Supplementary file 1. Study selection Two reviewers independently applied the inclusion criteria for assessment of eligibility, and the disagreements between reviewers were resolved by other authors. Articles were included if they met several criteria: (1) the study population was healthy Chinese population; (2) randomized controlled trials and observational studies on the safety or efficacy of varicella vaccine; and (3) the publication type is journal or conference paper. We excluded: (1) critical or review articles; (2) full text not available, (3) cost-effectiveness analysis and non-human study; (4) a sample size of less than 10; (5) clinical trials and study on post-exposure prophylaxis; and (6) key information was missing, such as sample size, number of vaccines administered, definition of antibody positive and positive transfer, antibody positive transfer rate, vaccine manufacturer, or number of systemic reactions and local reactions. Data extraction Two independent reviewers extracted the data, and all disagreements were resolved by consensus. The extracted information included: first author, year of publication, study design, study time period, inclusion and exclusion criteria, age, vaccine dose, sample size, mean or median age at vaccination, proportion of female, vaccine manufacturer, interval between vaccination and serum test, definition of seroconversion, serum sample size, the number of seroconversion cases in all populations, the number of susceptible populations, the number of seroconversion cases in susceptible populations, the number of non-susceptible populations, the number of seroconversion cases in non-susceptible populations, duration of safety observation, the number of systemic reactions and local reactions. In addition to the safety data, the number of fever and headache cases in systemic reactions and redness and swelling cases in local reactions were extracted. Quality assessment The quality of the included studies, for randomized controlled trials, was evaluated by two reviewers according to the modified Jadad Scale. Random sequence generation, randomization hiding, blind method and quitting and shedding were scored with a total score of 0–7. For cohort studies, we scored study population selection and outcome measures on a scale of 0–6 based on the Newcastle-Ottawa Scale (NOS). The scoring criteria for the two scales are provided in Supplementary file 2. Any disagreements were resolved by consensus or by consulting a third member of the team. Statistical analysis A random-effects meta-analysis model used to estimate the pooled proportion of seroconversion and adverse reactions. The computation of 95% confidence interval (CI) was combined with the Freeman-Tukey double arcsine transform of the proportions. Heterogeneity was assessed using the I 2 statistics, with values of > 50% indicating substantial inconsistency. The random effects models were used for pooled estimates when heterogeneity was greater than 50%, otherwise the fixed effects models were used for estimation. Subgroup analyses were used to explore the sources of heterogeneity in the study. Analyses were stratified by age, publication year, vaccine dose, manufacturer and quality score. Sensitivity analysis was used to eliminate each study one by one, and whether the overall effect size changed significantly before and after comparison. This meta-analysis procedure was accomplished using Stata 15.1 software. P value < 0.05 was considered statistically significant. Results Included studies A total of 1,553 articles were screened through search strategy (Fig. 1 ). After removal of duplicates, we screened 952 titles and abstracts for inclusion and reviewed the full texts of 142 studies. Finally, 34 articles met the inclusion and exclusion criteria, including 21 articles on immunogenicity [ 18 – 38 ] and 25 articles on safety [ 11 , 18 , 19 , 21 , 23 – 25 , 27 – 31 , 34 , 39 – 50 ]. Table 1 summarizes the characteristics of the selected studies. Of the 21 studies on immunogenicity, 11 were randomized controlled trials [ 18 , 21 , 22 , 24 , 25 , 27 – 29 , 32 , 35 , 37 ] and 10 were cohort studies [ 19 , 20 , 23 , 26 , 30 , 31 , 33 , 34 , 36 , 38 ]. Eighteen and seven studies evaluated the immunogenicity of 1 – [ 18 , 19 , 21 – 25 , 28 – 38 ] and 2-dose [ 20 , 22 , 23 , 26 , 27 , 31 , 38 ] Varv, respectively. Five articles evaluated the immunogenicity of imported Varv [ 18 , 22 , 25 , 32 , 35 ]. Of the 25 studies on safety, 11 were randomized controlled trials [ 11 , 18 , 21 , 24 , 25 , 27 – 29 , 39 , 44 , 48 ] and 14 were cohort studies [ 19 , 23 , 30 , 31 , 34 , 40 – 43 , 45 – 47 , 49 , 50 ]. Twenty-three studies evaluated the safety of 1 dose of Varv [ 18 , 19 , 21 , 23 – 25 , 28 – 31 , 34 , 39 – 50 ]; five studies evaluated the safety of 2 doses of Varv [ 11 , 23 , 27 , 31 , 45 ]. The safety of imported Varv was evaluated in 3 articles [ 18 , 25 , 48 ]. Immunogenicity of domestic Varv and imported Varv According to the random effects models, the pooled proportion of seroconversion in all populations after Varv vaccination was 89% (95%CI: 87%-92%). Studies showed high heterogeneity (I 2 = 97.03%, P < 0.001). The pooled seroconversion proportion of domestic Varv was 89% (95%CI: 86%-91%) and that of imported Varv was 93% (95%CI: 88%-98%) (Fig. 2 ). There was no statistically significant difference in proportion of seroconversion between domestic Varv and imported Varv (χ 2 = 1.97, P = 0.160). In susceptible populations, the pooled seroconversion proportion of domestic Varv was 96% (95%CI: 95%-97%). The pooled seroconversion proportion of imported Varv was 93% (95%CI: 87%-100%) (Fig. 3 ). In non-susceptible populations, the pooled seroconversion proportion of domestic Varv was 80% (93%CI: 75%-86%). The pooled seroconversion proportion of imported Varv was 81% (93%CI: 67%-96%) (Fig. 3 ). There was no statistically significant difference in proportion of seroconversion between domestic Varv and imported Varv in susceptible (χ 2 = 0.59, P = 0.440) and non-susceptible populations (χ 2 = 0.02, P = 0.900). Safety of domestic Varv and imported Varv According to the random effects models, the pooled proportion of systemic reactions was 11% (95%CI: 10%-13%), showing high heterogeneity (I 2 = 98.49%, P < 0.001). The pooled proportion of systemic reactions for domestic Varv was 11% (95%CI: 10%-13%). The pooled proportion of systemic reactions for imported Varv was 8% (95%CI: 6%-10%) (Fig. 4 ). The proportion of systemic reactions for domestic Varv was higher than that of imported Varv (χ 2 = 8.04, P < 0.001). The pooled proportions of fever and headache reactions in domestic Varv were 9% (95%CI: 8%-10%) and 1% (95%CI: 1%-1%), respectively (Supplementary file 3: Fig. S1; Fig. S2). The pooled proportions of fever and headache reactions of imported Varv were 6% (95%CI: 5%-8%) and 0% (95%CI: 0%-1%), respectively (Supplementary file 3: Fig. S1; Fig. S2). The pooled proportion of local reactions was 3% (95%CI: 2%-5%), showing high heterogeneity (I 2 = 94.32%, P < 0.001). The pooled proportion of local reactions for domestic Varv was 3% (95%CI: 2%-3%). The pooled proportion of local reactions for imported Varv was 7% (95%CI: 3%-10%) (Fig. 4 ). The proportion of systemic reactions for domestic Varv was lower than that of imported Varv (χ 2 = 5.30, P = 0.020). The pooled proportions of redness and swelling reactions of domestic Varv was 1% (95%CI: 1%-1%) and 1% (95%CI: 0%-1%), and the pooled proportions of redness and swelling reactions of imported Varv was 1% (95%CI: 0%-2%) and 1% (95%CI: 0%-1%) (Supplementary file 3: Fig. S3; Fig. S4). Quality assessment Of the 34 studies included, 15 randomized controlled trials had quality scores ranging from 2 to 7, with 5 having low scores (< 4) [ 24 , 28 , 32 , 37 , 48 ] and 10 having high scores (≥ 4) [ 11 , 18 , 21 , 22 , 25 , 27 , 29 , 35 , 39 , 44 ]. The quality scores of 19 cohort studies ranged from 2 to 6, with 4 scoring low (< 4) [ 26 , 34 , 47 , 50 ] and 15 scoring high (≥ 4 points) [ 19 , 20 , 23 , 30 , 31 , 33 , 36 , 38 , 40 – 43 , 45 , 46 , 49 ]. See Supplementary file 2 for details. Subgroup analyses Results revealed strong heterogeneity among the selected studies. To determine potential factors of heterogeneity, we conducted subgroup analyses as detailed in Table 2 and Table 3 . Because there are few studies on imported Varv, we performed subgroup analyses together with studies on domestic Varv. Subgroup analyses of immunogenicity showed a lower proportion of seroconversion in studies in 2015 and beyond (86%, 95%CI: 82%-89%) compared with studies prior to 2015 (95%, 95%CI: 93%-97%). According to the stratification of vaccine manufacturer, the pooled proportion of seroconversion in the vaccine studies of Changchun BCHT Biotechnology Co., Ltd. was higher (95%, 95%CI: 93%-98%), and the pooled proportion of seroconversion in the vaccine studies of Changchun Qijian Biological Products Co., Ltd. was lower (75%, 95%CI: 70%-80%). When stratified by study quality, high-quality studies had a lower proportion of seroconversion (87%, 95%CI: 84%-90%) compared with low-quality studies (95%, 95%CI: 92%-97%) (Table 2 ). Table 2 Subgroup analyses of immunogenicity based on literature publication year, vaccine doses, manufacturer and quality score Subgroup variable Number of Studies Serum sample size Proportion of seroconversion (95% CI) I 2 (%) Heterogeneity (χ 2 ) P value Interaction test (χ 2 ) P value Age ≤ 13 26 7,027 90 (88–92) 95.90 609.54 13 6 2,931 86 (78–94) 98.84 430.28 < 0.001 Publication year Before 2015 13 2,939 95 (93–97) 90.08 121.00 < 0.001 19.28 < 0.001 2015 and beyond 19 7,019 86 (82–89) 97.83 830.35 < 0.001 Vaccine doses 1 dose 22 6,485 91 (88–93) 95.81 501.73 < 0.001 2.04 0.150 2 doses 10 3,473 86 (81–92) 98.33 540.16 < 0.001 Vaccine manufacturer Shanghai Institute of Biological Products 9 1,913 88 (82–93) 93.21 117.90 < 0.001 58.33 < 0.001 Changchun Qijian Biological Products 5 2.021 75 (70–80) 84.31 25.50 < 0.001 Changchun BCHT Biotechnology 8 2,896 95 (93–98) 93.62 109.65 < 0.001 Other domestic manufacturers a 6 2,170 93 (90–97) 94.09 84.59 < 0.001 Glaxosmithkline Biologicals 4 958 91 (88–93) 95.38 64.88 < 0.001 Quality score < 4 9 2,431 95 (92–97) 92.42 105.51 < 0.001 12.90 < 0.001 ≥ 4 23 7,527 87 (84–90) 97.59 913.20 < 0.001 CI: confidence interval. a Other domestic manufacturer: Changchun Changsheng Biotechnology(1), Beijing Wantai Biological Pharmacy Enterprise (1), Changchun Institute of Biological Products(1), and Shanghai Rongsheng Bio-Pharmaceutical (3). Table 3 Subgroup analyses of safety based on literature publication year, vaccine doses, manufacturer and quality score Subgroup variable Number of Studies Serum sample size Proportion of reactions (95% CI) I 2 (%) Heterogeneity (χ 2 ) P value Interaction test (χ 2 ) P value Systemic reactions Age ≤ 13 36 28,381 10 (9–12) 98.39 2171.87 < 0.001 61.77 13 2 1,197 22 (19–24) - - - Publication year Before 2015 19 19,107 9 (7–11) 98.31 1065.02 < 0.001 7.25 0.010 2015 and beyond 19 10,471 14 (11–17) 98.67 1350.64 < 0.001 Vaccine doses 1 dose 30 24,991 11 (10–13) 98.49 1925.31 < 0.001 0.07 0.790 2 doses 8 4,587 10 (5–16) 98.50 466.64 < 0.001 Vaccine manufacturer Shanghai Institute of Biological Products 7 5,298 21 (10–32) 98.92 553.36 < 0.001 10.72 0.030 Changchun Qijian Biological Products 7 4,726 10 (4–17) 98.27 346.28 < 0.001 Changchun BCHT Biotechnology 12 13,521 8 (5–10) 97.18 389.43 < 0.001 Other domestic manufacturers a 10 5,312 13 (9–17) 98.68 682.71 < 0.001 Glaxosmithkline Biologicals 2 721 8 (6–10) - - - Quality score < 4 11 4,310 17 (11–23) 98.74 793.21 < 0.001 5.38 0.020 ≥ 4 27 25,268 9 (8–11) 98.37 1597.25 < 0.001 Local reactions Age ≤ 13 32 26,859 3 (2–3) 94.30 544.34 13 2 1,197 3 (2–4) - - - Publication year Before 2015 20 19,165 3 (2–3) 93.24 280.99 < 0.001 1.13 0.290 2015 and beyond 14 8,891 4 (2–5) 95.33 278.41 < 0.001 Vaccine doses 1 dose 29 24,381 2 (2–3) 93.06 403.73 < 0.001 13.20 < 0.001 2 doses 5 3,675 5 (4–6) 65.95 11.72 0.020 Vaccine manufacturer Shanghai Institute of Biological Products 7 5,298 3 (2–4) 76.52 25.55 < 0.001 7.07 0.130 Changchun Qijian Biological Products 5 4,033 3 (0–5) 92.91 56.45 < 0.001 Changchun BCHT Biotechnology 9 12,634 4 (2–6) 96.18 209.30 < 0.001 Other domestic manufacturers a 10 5,312 2 (1–3) 93.04 129.28 < 0.001 Glaxosmithkline Biologicals 3 779 7 (3–10) - - - Quality score < 4 10 4,023 4 (3–5) 77.85 40.63 < 0.001 7.85 0.010 ≥ 4 24 24,033 2 (2–3) 94.26 400.96 < 0.001 CI: confidence interval. a Other domestic manufacturer: Changchun Changsheng Biotechnology(2), Beijing Wantai Biological Pharmacy Enterprise (2), Changchun Institute of Biological Products(3), Shanghai Rongsheng Bio-Pharmaceutical (2), and Sinovac (Dalian) Vaccine Technology (1). For subgroup analyses of systemic reactions, there was a higher proportion of systemic with in studies in 2015 and beyond (14%, 95%CI: 11%-17%) compared with studies prior to 2015 (9%, 95%CI: 7%-11%). The pooled proportion of systemic reactions was higher in the vaccine studies of Shanghai Institute of Biological Products (21%, 95%CI: 10%-32%) and lower in the vaccine studies of Changchun BCHT Biotechnology (8%, 95%CI: 6%-10%). Higher quality studies had a lower proportion of systemic reactions (9%, 95%CI: 8%-11%) compared with lower quality studies (17%, 95%CI: 11%-23%) (Table 3 ). Sensitivity analysis showed that omission of any single studies did not significantly change the overall estimate, which indicated that our analysis was stable. Discussion In this study, we analyzed the immunogenicity of domestic Varv and imported Varv in healthy Chinese population. In our analysis that included 16,655 Chinese people from 21 studies, both the domestic Varv and imported Varv were highly immunogenic. The serum conversion proportion of domestic Varv (89%) was lower than that of imported Varv (93%), but this difference was not statistically significant. The proportion of seroconversion in this study was slightly lower than that of healthy individuals who received Varv in previous studies (≥ 95%) [ 51 , 52 ]. However, it was higher than the 88% seroconversion proportion found in pediatric solid organ transplant recipients [ 53 ]. This may be due to differences in serologic assays. Serum samples included in our study were tested using fluorescent antibody-to-membrane antigen. Enzyme immunoassay and enzyme-linked immunosorbent assays that were used in previous studies may not have sufficient sensitivity to detect antibodies after vaccination (generally ranging between 74% and 99%, depending on the assay used), which could lead to outcome misclassification bias [ 53 ]. The serologic test method should be taken into account when interpreting the immunogenicity outcome of seroconversion. Of course, different population may also cause differences in seroconversion after vaccination. When we further classified domestic vaccine manufacturers, we found differences in immunogenicity among different manufacturers. The immunogenicity of Varv produced by five manufacturers, including Changchun BCHT Biotechnology and Changchun Changsheng Biotechnology Co., LTD was better than that of Varv produced by GlaxoSmithKline Biologics. There was considerable heterogeneity among the studies within each group of manufacturers, and the results need to be interpreted with caution. In addition, the imported vaccines in this study were all produced by GlaxoSmithKline Biologics in Belgium. Studies of other imported vaccines, such as those from Merck in the United States, were lacking. Future studies can also further demonstrate the differences in immunogenicity between domestic Varv and imported Varv. In our safety analysis that included 29,696 Chinese people from 25 studies, the proportion of systemic reactions to the domestic Varv was higher than that of the imported Varv; the proportion of local reactions of domestic Varv was lower than that of imported Varv. The results of subgroup analyses in different manufacturers are consistent. Our findings on local reactions are also consistent with previous studies [ 22 , 54 ]. This suggests that there may be differences in the safety profiles of domestic and imported Varv vaccines in Chinese populations. Further research is needed to determine the underlying reasons for these differences and to ensure the safety and efficacy of Varv vaccines for all individuals. In short, the study found that both domestic and imported varicella vaccines are effective and safe in the Chinese population. The domestic vaccine is more affordable but may have limitations in terms of performance. The imported vaccine, while more expensive and requiring cold chain transportation, may face challenges in large-scale implementation. Overall, both vaccines have their advantages and limitations, and public health efforts should consider these factors when promoting varicella vaccination in China. The study showed that a lower proportion of systemic reactions was observed in individuals aged 13 years old or younger compared to those over 13 years old. This finding suggests that younger individuals may have a lower risk of experiencing systemic reactions following varicella vaccination compared to older individuals. This is consistent with previous findings in people living with HIV [ 55 ]. The statement that there are fewer studies on the use of the varicella vaccine in adults compared to children highlights an important gap in current research. While varicella vaccination is commonly administered to children as part of routine immunization schedules, there is less data available on the safety and efficacy of the vaccine in adults. More studies are indeed needed in the future to demonstrate the safety and effectiveness of varicella vaccination in adults. These studies could help inform public health policies regarding the use of varicella vaccine in adult populations, especially those at higher risk of complications from varicella infection. Additionally, further research could provide valuable insights into the potential benefits of vaccinating adults against varicella, such as reducing the overall burden of varicella-related illness and complications in the population [ 4 ]. We also found that the proportion of local reactions with two doses of Varv was higher than with one dose. Similar results were observed in previous meta-analysis, where local reactions tended to be stronger after a second dose of varicella vaccine [ 56 ]. Local reactions are indeed the most common type of reactions following vaccination. These reactions typically include redness and swelling at the injection site and are generally mild and self-limited [ 57 ]. The higher proportion of local reactions with two doses of varicella vaccine could be due to a variety of factors, including increased immune response with the second dose or individual variability in reactions. While these reactions are typically not cause for concern, healthcare providers should be aware of this finding and monitor patients accordingly after vaccination. Previous studies have also found a lower incidence of systemic reactions (such as fever or headache) after the second dose compared to the first dose [ 56 , 58 ]. Similar findings were found in this study, but were not statistically significant. Several limitations of the present study must be acknowledged. First, the relatively small number of study on imported varicella vaccine probably leads to inaccurate evaluation of results, and also make it impossible to conduct separate subgroup analyses of domestic and imported vaccines in this study. Second, there was substantial heterogeneity in the immunogenicity and safety outcomes, which attests to important variation between the included studies. Heterogeneity did not decrease after our subgroup analyses. However, the results of sensitivity analysis showed that the immunogenicity and safety values were reliable. Conclusions In conclusion, both domestically produced and imported varicella vaccines had high immunogenicity. Some differences in the types and frequencies of reactions observed. The proportion of systemic reactions was higher with domestic Varv, while the proportion of local reactions was higher with imported Varv. Overall, both domestic and imported varicella vaccines are considered safe and effective in preventing chickenpox, and individuals should follow the recommendations of healthcare providers and public health authorities regarding vaccination. Abbreviations VZV Varicella zoster virus VarV Live-attenuated varicella vaccine CNKI China National Knowledge Internet SinoMed Chinese Biomedical Literature Service System NOS Newcastle-Ottawa Scale CI Confidence interval Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Availability of data and materials The data set supporting this article is available on demand to the corresponding author. Competing interests The authors declare no competing interests. Funding This study was supported by the Postdoctoral Fellowship Program of CPSF (Grant Number, GZB20230037), and National Social Science Fund of China (Grant Number, 21&ZD187). Authors’ contributions Y.Y. and P.H. contributed to conception. Y.Y., T.W., Y.X., Z.S., and P.H. contributed to design. Y.Y. and T.W. contributed to search strategy. Y.Y., T.W., and Y.X. did study selection based on title, abstract and full text; and data extraction. Y.Y. and Z.S. contributed to data synthesis and analysis and article drafting. Y.Y. and P.H. contributed to data interpretation, article revision and review. All authors read and approved the final article. Acknowledgements Not applicable. 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Med Innov Chin 7:9–11 Lu X, Zhou W, Gu K et al (2008) Safety and immunogenicity of Changsheng Technology freeze-dried live attenuated varicella vaccine. J Southeast Univ (Medical Sci Edition) 27:207–211 Luo L, Liu X, Ma Y et al (2016) Safety and immunogenicity of freeze-dried live attenuated varicella vaccine. Chin J Biol 29:1298–1300 Luo S, Jiang D, Huang Y et al (2019) Immunogenicity and safety of two-dose and booster immunization schedules of domestic varicella vaccine. Chin J Biol 32:1381–1385 Ma R, Xu G, Pan X et al (2012) Observation on immunogenicity of domestic freeze-dried live attenuated varicella vaccine and immunity persistence one year after vaccination. Dis Surveill 27:601–603 Shen Y, Lu J, Chen H (2007) Observation on the level of varicella immunity in children in kindergarten and the effect of domestic varicella vaccine. Chin J Public Health Manage 23:72–73 Sun H, Fang H, Li R et al (2009) Adverse Reaction and Immunogenicity Induced by Freeze-dried Live Attenuated Varicella Vaccine. Chin J Biol 22:702–704 Tang Y, Du F, Chen H et al (2014) Post-Marketing Immunogenicity and Safety of Two Different Live Attemuatal Varicella Vaccine. Chin J Vaccin Immuniz 20:241–244 Wang Q, Li Y, Wang L (2017) Safety and immunogenicity of lyophilized live attenuated varicella vaccine in children aged 1–6 years. Prev Med 29:711–713 Wang Z, Xiao Q, Li F et al (2011) Safety and Immunological Effect of Domestic Varicella Attenuated Live Vaccine (Freeze-dried). Chin J Vaccin Immuniz 17:531–534 Zhang Q, Fei J, Zhong P et al (2017) Study on safety and immunogenicity of domestic freeze-dried live attenuated varicella vaccine with 2 doses. Sh Prev Med 29:59–61 Bai Y, Yang L, Guo L et al (2011) Safety and Immunogenicity of Gelatin-free Freeze-dried Live Attenuated Varicella Vaccine. Chin J Biol 24:1336–1338 Cai Z (2012) Observation on reaction and immune effect of lyophilized live attenuated varicella vaccine. Med Inf 25:279–280 Hu H (2015) Evaluation of safety and immunogenicity of lyophilized live attenuated varicella vaccine. Med Inf 28:311 Jiang Z, Chen E, Li Q et al (2009) Observation on Side Effect of the Domestic Lyophilized Live Attenuated Varicella Vaccine. Zh Prev Med 21:12–13 Li Y, Gao Z, Tao H et al (2012) Safety of freeze-dried live attenuated varicella vaccine. Chin J Biol 25:1667–1670 Mo ZJ, Huang SJ, Qiu LX et al (2023) Safety and immunogenicity of a skin- and neuro-attenuated live vaccine for varicella: a randomized, double-blind, controlled, dose-escalation and age de-escalation phase 1 clinical trial. Lancet Reg Health West Pac 34:100707 Peng S, Liao Z, Wan X et al (2018) Safety of Chinese freeze - dried varicella attenuated live vaccine. J Med Pest Control 34:428–431 Shen Y, Jiang X, Gu X et al (2003) Inoculation reaction and immune effect of domestic freeze-dried live attenuated varicella vaccine. Chin J Biol 16:314–315 Sun H, Yuan J, Liu X (2003) Immunogenicity and cost-effectiveness analysis of domestic varicella vaccine. Sh J Prev Med 15:445–447 Tang Y, Su J, Xia Y et al (2012) Safety and immunogenicity of domestic gelatin-free freeze-dried live attenuated varicella vaccine. Chin J Biol 25:1516–1519 Wang F, Chen Z, Chen X (2006) Observation on efficacy of live attenuated varicella vaccine in Weifang City. Med Anim Control 22:813–814 Wang L, Liu Y, Li L et al (2003) Observation on immune effect of domestic freeze-dried live attenuated varicella vaccine. South China J Prev Med 29:30–31 Shinefield HR, Black SB, Staehle BO et al (2002) Vaccination with measles, mumps and rubella vaccine and varicella vaccine: safety, tolerability, immunogenicity, persistence of antibody and duration of protection against varicella in healthy children. Pediatr Infect Dis J 21:555–561 National Advisory Committee on Immunization (NACI) Varicella (chicken pox) vaccine: Canadian Immunization Guide [internet]. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-24-varicella-chickenpox-vaccine.html Piché-Renaud PP, Yue Lee E, Ji C et al (2023) Safety and immunogenicity of the live-attenuated varicella vaccine in pediatric solid organ transplant recipients: A systematic review and meta-analysis. Am J Transpl 23:1757–1770 Shi X (2019) Comparative study on immune effect of domestic and imported varicella vaccine. Electron J Clin Med Literature 6:176 Carta V, Mangeri L, Tiecco G et al (2024) Immunogenicity and safety of live attenuated and recombinant/inactivated varicella zoster vaccines in people living with HIV: A systematic review. Hum Vaccin Immunother 20:2341456 Yin M, Xu X, Liang Y et al (2018) Effectiveness, immunogenicity and safety of one vs. two-dose varicella vaccination: a meta-analysis. Expert Rev Vaccines 17:351–362 Su JR, Leroy Z, Lewis PW et al (2017) Safety of Second-Dose Single-Antigen Varicella Vaccine. Pediatrics. ;139 Kuter BJ, Brown M, Wiedmann RT et al (2016) Safety and Immunogenicity of M-M-RII (Combination Measles-Mumps-Rubella Vaccine) in Clinical Trials of Healthy Children Conducted Between 1988 and 2009. Pediatr Infect Dis J 35:1011–1020 Tables Table 1 is available in the Supplementary Files section. Additional Declarations The authors declare no competing interests. Supplementary Files Supplementaryfile1.doc Supplementaryfile2.doc Supplementaryfile3.doc Supplementaryfile4.doc Table1.docx Cite Share Download PDF Status: Posted Version 1 posted 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-5061401","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":351815864,"identity":"1554e6dc-f1bb-4b84-84bc-5d8abf71f35e","order_by":0,"name":"Yemin Yuan","email":"","orcid":"","institution":"Peking University","correspondingAuthor":false,"prefix":"","firstName":"Yemin","middleName":"","lastName":"Yuan","suffix":""},{"id":351893831,"identity":"e488fc4b-81f5-4c0e-a64b-a03fa75ba4bd","order_by":1,"name":"Tong Wang","email":"","orcid":"","institution":"Qingdao Municipal 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studies.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5061401/v1/76ea73cb05ff786b07c53547.png"},{"id":64267221,"identity":"c929ec9c-c003-48bd-9ca5-8d83e27b8c4e","added_by":"auto","created_at":"2024-09-11 04:27:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":90161,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot for the proportion of seroconversion in all populations.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5061401/v1/d6feea46d68905741ae5b047.png"},{"id":64267222,"identity":"40ff91a7-9673-4fe2-b5fb-eaa34eeb25f5","added_by":"auto","created_at":"2024-09-11 04:27:53","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":373053,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot for the proportion of seroconversion in susceptible populations\u0026nbsp;and non-susceptible populations.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-5061401/v1/85b502c3d8e1b9e29a46464a.png"},{"id":64267224,"identity":"cf2b4691-4833-4d8c-b072-3457e42e14fd","added_by":"auto","created_at":"2024-09-11 04:27:53","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":467591,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot for the proportion of systemic and local reactions.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-5061401/v1/4c0a8538544dab4646ecb7a9.png"},{"id":64268348,"identity":"561a6e60-c524-4931-a0e3-0f4f8abc512b","added_by":"auto","created_at":"2024-09-11 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04:27:54","extension":"doc","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":204800,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaryfile2.doc","url":"https://assets-eu.researchsquare.com/files/rs-5061401/v1/05bcbf6f4b616a7c331fa686.doc"},{"id":64267226,"identity":"e66676af-c392-445e-8363-5107408137d5","added_by":"auto","created_at":"2024-09-11 04:27:53","extension":"doc","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":349696,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaryfile3.doc","url":"https://assets-eu.researchsquare.com/files/rs-5061401/v1/016c825efde6c46cc98e3e11.doc"},{"id":64268347,"identity":"49814f56-a912-49bf-8e0d-91b4205b36df","added_by":"auto","created_at":"2024-09-11 04:43:53","extension":"doc","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":60416,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaryfile4.doc","url":"https://assets-eu.researchsquare.com/files/rs-5061401/v1/46084da108a9b19e3cd9a94b.doc"},{"id":64267227,"identity":"6b1a16ac-7b2b-4fcc-ad20-561c26f012e4","added_by":"auto","created_at":"2024-09-11 04:27:54","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":34731,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-5061401/v1/800180a0322a00c07981b454.docx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eImmunogenicity and safety of the domestic and imported live-attenuated varicella vaccine in healthy Chinese population: A systematic review and meta-analysis\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eVaricella (chickenpox) is an infectious disease caused by the varicella zoster virus (VZV) affecting children, adolescents, and adults [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Varicella is very contagious through its transmission by direct contact with vesicular skin lesions that contain high titers of infectious virus and respiratory droplets, which is prevalent globally and has a substantial disease burden [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The annual global burden of varicella was estimated to be around 140\u0026nbsp;million cases with 4.2\u0026nbsp;million severe complications requiring hospitalisation, and 4,200 deaths [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Primary healthcare visits for varicella accounted for 30%-85% of total direct costs; hospitalization costs ranged from \u003cspan\u003e$\u003c/span\u003e1,308 to \u003cspan\u003e$\u003c/span\u003e38,268 per episode, contributing between 2% and 60% to total direct costs [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Recently, the incidence of varicella has increased significantly in China. The reported incidence of varicella increased from 3.17/100,000 (41,211 cases) to 70.14/100,000 (979,482 cases) during the period 2005\u0026ndash;2019 [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. A total of 10,446 varicella public health emergency events were reported in China from 2007 to 2021, with 261 (in 2012) to 1,327 (in 2018) reported annually [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eVaccination is the most effective approach against varicella. In the United States and Japan, since the implementation of varicella vaccination program, the incidence of varicella has decreased substantially [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], as has the hospitalization and mortality rate [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Currently, varicella vaccine has not been included in national immunization programmes in China [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The average chickenpox vaccination rate in China was 61.1% (95%CI: 55.7%-66.5%) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], which was significantly lower than that in Spain, Italy, Germany and other countries that included chickenpox vaccine in national or regional immunization programmes [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Moreover, the positive rate of VZV IgG antibody in healthy population in China was low (64%, 95%CI: 60%-67%) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWorldwide, there are several formulations of varicella vaccines; all contain live attenuated VZV, and all, except the vaccine licensed in South Korea, are based on the Oka strain of VZV isolated in Japan [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Imported live-attenuated varicella vaccine (VarV) began to be introduced into China in 1997, and after 2001, a number of domestic VarV was also developed and made available. In the application of VarV, managers, doctors, vaccine recipients, and parents have concerns about the safety and immunogenicity of domestic VarV. Additionally, the cost of imported varicella vaccine is often higher than domestic options, which can limit the widespread adoption and promotion of varicella vaccination in China.\u003c/p\u003e \u003cp\u003eTherefore, this study used systematic review and meta-analysis to comprehensively analyze the published data of domestic Varv and imported VarV in Chinese population in recent years. This study aimed to compare the immunogenicity and safety of domestic Varv and imported VarV, and to provide reference for the further application of VarV in Chinese population.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eWe performed a systematic review and meta-analysis using PRISMA guidelines [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The protocol was registered on PROSPERO (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e\u003ca href=\"http://www.crd.york.ac.uk/prospero/\" target=\"_blank\"\u003ewww.crd.york.ac.uk/prospero/\u003c/a\u003e\u003c/span\u003e\u003cspan address=\"http://www.crd.york.ac.uk/prospero/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e; identifier CRD42024546352).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSearch strategy\u003c/h2\u003e \u003cp\u003eWe searched PubMed, Web of Science, Embase, China National Knowledge Internet (CNKI), Wan Fang Database, Chinese Biomedical Literature Service System (SinoMed) databases for articles until March 15, 2024 in any language. The following terms were used in different combinations and constructions depending on the applied database. We used search terms including \u0026ldquo;varicella zoster virus infection\u0026rdquo;, \u0026ldquo;varicella\u0026rdquo;, \u0026ldquo;chickenpox\u0026rdquo;, \u0026ldquo;immunization\u0026rdquo;, \u0026ldquo;vaccination\u0026rdquo;, \u0026ldquo; chickenpox vaccine\u0026rdquo;, \u0026ldquo;vaccines\u0026rdquo;, \u0026ldquo;vaccine\u0026rdquo;, \u0026ldquo;safety\u0026rdquo;, \u0026ldquo;security\u0026rdquo;, \u0026ldquo;adverse effect\u0026rdquo;, \u0026ldquo;adverse reaction\u0026rdquo;, \u0026ldquo;side effect\u0026rdquo;, \u0026ldquo;side-effect\u0026rdquo;, \u0026ldquo;side reaction\u0026rdquo;, \u0026ldquo;immunogenicity\u0026rdquo;, \u0026ldquo;efficacy\u0026rdquo;, \u0026ldquo;potency\u0026rdquo;, \u0026ldquo;effectiveness\u0026rdquo;, and \u0026ldquo;effect\u0026rdquo;. \u0026ldquo;China\u0026rdquo; or \u0026ldquo;Chinese\u0026rdquo; were used when searching for English articles to identify articles that presented data on immunogenicity and safety in Chinese population. Details of the complete search strategy are available in Supplementary file 1.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy selection\u003c/h2\u003e \u003cp\u003eTwo reviewers independently applied the inclusion criteria for assessment of eligibility, and the disagreements between reviewers were resolved by other authors. Articles were included if they met several criteria: (1) the study population was healthy Chinese population; (2) randomized controlled trials and observational studies on the safety or efficacy of varicella vaccine; and (3) the publication type is journal or conference paper. We excluded: (1) critical or review articles; (2) full text not available, (3) cost-effectiveness analysis and non-human study; (4) a sample size of less than 10; (5) clinical trials and study on post-exposure prophylaxis; and (6) key information was missing, such as sample size, number of vaccines administered, definition of antibody positive and positive transfer, antibody positive transfer rate, vaccine manufacturer, or number of systemic reactions and local reactions.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eData extraction\u003c/h2\u003e \u003cp\u003eTwo independent reviewers extracted the data, and all disagreements were resolved by consensus. The extracted information included: first author, year of publication, study design, study time period, inclusion and exclusion criteria, age, vaccine dose, sample size, mean or median age at vaccination, proportion of female, vaccine manufacturer, interval between vaccination and serum test, definition of seroconversion, serum sample size, the number of seroconversion cases in all populations, the number of susceptible populations, the number of seroconversion cases in susceptible populations, the number of non-susceptible populations, the number of seroconversion cases in non-susceptible populations, duration of safety observation, the number of systemic reactions and local reactions. In addition to the safety data, the number of fever and headache cases in systemic reactions and redness and swelling cases in local reactions were extracted.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eQuality assessment\u003c/h2\u003e \u003cp\u003eThe quality of the included studies, for randomized controlled trials, was evaluated by two reviewers according to the modified Jadad Scale. Random sequence generation, randomization hiding, blind method and quitting and shedding were scored with a total score of 0\u0026ndash;7. For cohort studies, we scored study population selection and outcome measures on a scale of 0\u0026ndash;6 based on the Newcastle-Ottawa Scale (NOS). The scoring criteria for the two scales are provided in Supplementary file 2. Any disagreements were resolved by consensus or by consulting a third member of the team.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eA random-effects meta-analysis model used to estimate the pooled proportion of seroconversion and adverse reactions. The computation of 95% confidence interval (CI) was combined with the Freeman-Tukey double arcsine transform of the proportions. Heterogeneity was assessed using the I\u003csup\u003e2\u003c/sup\u003e statistics, with values of \u0026gt;\u0026thinsp;50% indicating substantial inconsistency. The random effects models were used for pooled estimates when heterogeneity was greater than 50%, otherwise the fixed effects models were used for estimation. Subgroup analyses were used to explore the sources of heterogeneity in the study. Analyses were stratified by age, publication year, vaccine dose, manufacturer and quality score. Sensitivity analysis was used to eliminate each study one by one, and whether the overall effect size changed significantly before and after comparison. This meta-analysis procedure was accomplished using Stata 15.1 software. \u003cem\u003eP\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eIncluded studies\u003c/h2\u003e \u003cp\u003eA total of 1,553 articles were screened through search strategy (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). After removal of duplicates, we screened 952 titles and abstracts for inclusion and reviewed the full texts of 142 studies. Finally, 34 articles met the inclusion and exclusion criteria, including 21 articles on immunogenicity [\u003cspan additionalcitationids=\"CR19 CR20 CR21 CR22 CR23 CR24 CR25 CR26 CR27 CR28 CR29 CR30 CR31 CR32 CR33 CR34 CR35 CR36 CR37\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e] and 25 articles on safety [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan additionalcitationids=\"CR28 CR29 CR30\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan additionalcitationids=\"CR40 CR41 CR42 CR43 CR44 CR45 CR46 CR47 CR48 CR49\" citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes the characteristics of the selected studies. Of the 21 studies on immunogenicity, 11 were randomized controlled trials [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan additionalcitationids=\"CR28\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e] and 10 were cohort studies [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Eighteen and seven studies evaluated the immunogenicity of 1 \u0026ndash; [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan additionalcitationids=\"CR22 CR23 CR24\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan additionalcitationids=\"CR29 CR30 CR31 CR32 CR33 CR34 CR35 CR36 CR37\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e] and 2-dose [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e] Varv, respectively. Five articles evaluated the immunogenicity of imported Varv [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Of the 25 studies on safety, 11 were randomized controlled trials [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan additionalcitationids=\"CR28\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e] and 14 were cohort studies [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan additionalcitationids=\"CR41 CR42\" citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan additionalcitationids=\"CR46\" citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e, \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. Twenty-three studies evaluated the safety of 1 dose of Varv [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan additionalcitationids=\"CR29 CR30\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan additionalcitationids=\"CR40 CR41 CR42 CR43 CR44 CR45 CR46 CR47 CR48 CR49\" citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]; five studies evaluated the safety of 2 doses of Varv [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. The safety of imported Varv was evaluated in 3 articles [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eImmunogenicity of domestic Varv and imported Varv\u003c/h2\u003e \u003cp\u003eAccording to the random effects models, the pooled proportion of seroconversion in all populations after Varv vaccination was 89% (95%CI: 87%-92%). Studies showed high heterogeneity (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;97.03%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The pooled seroconversion proportion of domestic Varv was 89% (95%CI: 86%-91%) and that of imported Varv was 93% (95%CI: 88%-98%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). There was no statistically significant difference in proportion of seroconversion between domestic Varv and imported Varv (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;1.97, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.160).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn susceptible populations, the pooled seroconversion proportion of domestic Varv was 96% (95%CI: 95%-97%). The pooled seroconversion proportion of imported Varv was 93% (95%CI: 87%-100%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In non-susceptible populations, the pooled seroconversion proportion of domestic Varv was 80% (93%CI: 75%-86%). The pooled seroconversion proportion of imported Varv was 81% (93%CI: 67%-96%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). There was no statistically significant difference in proportion of seroconversion between domestic Varv and imported Varv in susceptible (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.59, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.440) and non-susceptible populations (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.02, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.900).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSafety of domestic Varv and imported Varv\u003c/h2\u003e \u003cp\u003eAccording to the random effects models, the pooled proportion of systemic reactions was 11% (95%CI: 10%-13%), showing high heterogeneity (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;98.49%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The pooled proportion of systemic reactions for domestic Varv was 11% (95%CI: 10%-13%). The pooled proportion of systemic reactions for imported Varv was 8% (95%CI: 6%-10%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The proportion of systemic reactions for domestic Varv was higher than that of imported Varv (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;8.04, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The pooled proportions of fever and headache reactions in domestic Varv were 9% (95%CI: 8%-10%) and 1% (95%CI: 1%-1%), respectively (Supplementary file 3: Fig. S1; Fig. S2). The pooled proportions of fever and headache reactions of imported Varv were 6% (95%CI: 5%-8%) and 0% (95%CI: 0%-1%), respectively (Supplementary file 3: Fig. S1; Fig. S2).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe pooled proportion of local reactions was 3% (95%CI: 2%-5%), showing high heterogeneity (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;94.32%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The pooled proportion of local reactions for domestic Varv was 3% (95%CI: 2%-3%). The pooled proportion of local reactions for imported Varv was 7% (95%CI: 3%-10%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The proportion of systemic reactions for domestic Varv was lower than that of imported Varv (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;5.30, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.020). The pooled proportions of redness and swelling reactions of domestic Varv was 1% (95%CI: 1%-1%) and 1% (95%CI: 0%-1%), and the pooled proportions of redness and swelling reactions of imported Varv was 1% (95%CI: 0%-2%) and 1% (95%CI: 0%-1%) (Supplementary file 3: Fig. S3; Fig. S4).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eQuality assessment\u003c/h2\u003e \u003cp\u003eOf the 34 studies included, 15 randomized controlled trials had quality scores ranging from 2 to 7, with 5 having low scores (\u0026lt;\u0026thinsp;4) [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e] and 10 having high scores (\u0026ge;\u0026thinsp;4) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. The quality scores of 19 cohort studies ranged from 2 to 6, with 4 scoring low (\u0026lt;\u0026thinsp;4) [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e] and 15 scoring high (\u0026ge;\u0026thinsp;4 points) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan additionalcitationids=\"CR41 CR42\" citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e, \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e, \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. See Supplementary file 2 for details.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eSubgroup analyses\u003c/h2\u003e \u003cp\u003eResults revealed strong heterogeneity among the selected studies. To determine potential factors of heterogeneity, we conducted subgroup analyses as detailed in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Because there are few studies on imported Varv, we performed subgroup analyses together with studies on domestic Varv. Subgroup analyses of immunogenicity showed a lower proportion of seroconversion in studies in 2015 and beyond (86%, 95%CI: 82%-89%) compared with studies prior to 2015 (95%, 95%CI: 93%-97%). According to the stratification of vaccine manufacturer, the pooled proportion of seroconversion in the vaccine studies of Changchun BCHT Biotechnology Co., Ltd. was higher (95%, 95%CI: 93%-98%), and the pooled proportion of seroconversion in the vaccine studies of Changchun Qijian Biological Products Co., Ltd. was lower (75%, 95%CI: 70%-80%). When stratified by study quality, high-quality studies had a lower proportion of seroconversion (87%, 95%CI: 84%-90%) compared with low-quality studies (95%, 95%CI: 92%-97%) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\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\u003eSubgroup analyses of immunogenicity based on literature publication year, vaccine doses, manufacturer and quality score\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\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=\"left\" 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=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSubgroup variable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNumber of Studies\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSerum sample size\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eProportion of seroconversion\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eI\u003csup\u003e2\u003c/sup\u003e (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHeterogeneity (χ\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eInteraction test (χ\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7,027\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e90 (88\u0026ndash;92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e95.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e609.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.400\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\u0026gt;\u0026thinsp;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,931\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e86 (78\u0026ndash;94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e98.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e430.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePublication year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBefore 2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,939\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95 (93\u0026ndash;97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e90.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e121.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e19.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\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\u003e2015 and beyond\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7,019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e86 (82\u0026ndash;89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e97.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e830.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVaccine doses\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6,485\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e91 (88\u0026ndash;93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e95.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e501.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e2.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.150\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\u003e2 doses\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3,473\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e86 (81\u0026ndash;92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e98.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e540.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVaccine manufacturer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eShanghai Institute of Biological Products\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,913\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e88 (82\u0026ndash;93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e93.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e117.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e58.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\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\u003eChangchun Qijian Biological Products\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e75 (70\u0026ndash;80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e84.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e25.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\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\u003eChangchun BCHT Biotechnology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,896\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95 (93\u0026ndash;98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e93.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e109.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\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\u003eOther domestic manufacturers\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e93 (90\u0026ndash;97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e94.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e84.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\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\u003eGlaxosmithkline Biologicals\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e958\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e91 (88\u0026ndash;93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e95.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e64.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQuality score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,431\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95 (92\u0026ndash;97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e92.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e105.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e12.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\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\u0026ge;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7,527\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e87 (84\u0026ndash;90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e97.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e913.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003eCI: confidence interval. \u003csup\u003ea\u003c/sup\u003eOther domestic manufacturer: Changchun Changsheng Biotechnology(1), Beijing Wantai Biological Pharmacy Enterprise (1), Changchun Institute of Biological Products(1), and Shanghai Rongsheng Bio-Pharmaceutical (3).\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \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\u003eSubgroup analyses of safety based on literature publication year, vaccine doses, manufacturer and quality score\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\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=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSubgroup variable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNumber of Studies\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSerum sample size\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eProportion of reactions (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eI\u003csup\u003e2\u003c/sup\u003e (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHeterogeneity (χ\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eInteraction test (χ\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"10\" nameend=\"c10\" namest=\"c1\"\u003e \u003cp\u003eSystemic reactions\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28,381\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (9\u0026ndash;12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e98.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2171.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e61.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\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\u0026gt;\u0026thinsp;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,197\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22 (19\u0026ndash;24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePublication year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBefore 2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19,107\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9 (7\u0026ndash;11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e98.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1065.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.010\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\u003e2015 and beyond\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10,471\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14 (11\u0026ndash;17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e98.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1350.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVaccine doses\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24,991\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11 (10\u0026ndash;13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e98.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1925.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.790\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\u003e2 doses\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,587\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (5\u0026ndash;16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e98.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e466.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVaccine manufacturer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eShanghai Institute of Biological Products\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5,298\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21 (10\u0026ndash;32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e98.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e553.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e10.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.030\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\u003eChangchun Qijian Biological Products\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,726\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (4\u0026ndash;17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e98.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e346.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\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\u003eChangchun BCHT Biotechnology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13,521\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 (5\u0026ndash;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e97.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e389.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\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\u003eOther domestic manufacturers\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5,312\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13 (9\u0026ndash;17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e98.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e682.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\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\u003eGlaxosmithkline Biologicals\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e721\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 (6\u0026ndash;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQuality score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,310\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17 (11\u0026ndash;23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e98.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e793.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.020\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\u0026ge;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25,268\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9 (8\u0026ndash;11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e98.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1597.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"10\" nameend=\"c10\" namest=\"c1\"\u003e \u003cp\u003eLocal reactions\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26,859\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (2\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e94.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e544.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.250\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\u0026gt;\u0026thinsp;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,197\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (2\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePublication year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBefore 2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19,165\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (2\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e93.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e280.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.290\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\u003e2015 and beyond\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8,891\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (2\u0026ndash;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e95.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e278.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVaccine doses\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24,381\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (2\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e93.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e403.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e13.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\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\u003e2 doses\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3,675\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (4\u0026ndash;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e65.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e11.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVaccine manufacturer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eShanghai Institute of Biological Products\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5,298\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (2\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e76.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e25.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.130\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\u003eChangchun Qijian Biological Products\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,033\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (0\u0026ndash;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e92.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e56.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\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\u003eChangchun BCHT Biotechnology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12,634\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (2\u0026ndash;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e96.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e209.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\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\u003eOther domestic manufacturers\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5,312\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (1\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e93.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e129.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\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\u003eGlaxosmithkline Biologicals\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e779\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (3\u0026ndash;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQuality score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (3\u0026ndash;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e77.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e40.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.010\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\u0026ge;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24,033\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (2\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e94.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e400.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003eCI: confidence interval. \u003csup\u003ea\u003c/sup\u003eOther domestic manufacturer: Changchun Changsheng Biotechnology(2), Beijing Wantai Biological Pharmacy Enterprise (2), Changchun Institute of Biological Products(3), Shanghai Rongsheng Bio-Pharmaceutical (2), and Sinovac (Dalian) Vaccine Technology (1).\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFor subgroup analyses of systemic reactions, there was a higher proportion of systemic with in studies in 2015 and beyond (14%, 95%CI: 11%-17%) compared with studies prior to 2015 (9%, 95%CI: 7%-11%). The pooled proportion of systemic reactions was higher in the vaccine studies of Shanghai Institute of Biological Products (21%, 95%CI: 10%-32%) and lower in the vaccine studies of Changchun BCHT Biotechnology (8%, 95%CI: 6%-10%). Higher quality studies had a lower proportion of systemic reactions (9%, 95%CI: 8%-11%) compared with lower quality studies (17%, 95%CI: 11%-23%) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Sensitivity analysis showed that omission of any single studies did not significantly change the overall estimate, which indicated that our analysis was stable.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we analyzed the immunogenicity of domestic Varv and imported Varv in healthy Chinese population. In our analysis that included 16,655 Chinese people from 21 studies, both the domestic Varv and imported Varv were highly immunogenic. The serum conversion proportion of domestic Varv (89%) was lower than that of imported Varv (93%), but this difference was not statistically significant. The proportion of seroconversion in this study was slightly lower than that of healthy individuals who received Varv in previous studies (\u0026ge;\u0026thinsp;95%) [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e, \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. However, it was higher than the 88% seroconversion proportion found in pediatric solid organ transplant recipients [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. This may be due to differences in serologic assays. Serum samples included in our study were tested using fluorescent antibody-to-membrane antigen. Enzyme immunoassay and enzyme-linked immunosorbent assays that were used in previous studies may not have sufficient sensitivity to detect antibodies after vaccination (generally ranging between 74% and 99%, depending on the assay used), which could lead to outcome misclassification bias [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. The serologic test method should be taken into account when interpreting the immunogenicity outcome of seroconversion. Of course, different population may also cause differences in seroconversion after vaccination.\u003c/p\u003e \u003cp\u003eWhen we further classified domestic vaccine manufacturers, we found differences in immunogenicity among different manufacturers. The immunogenicity of Varv produced by five manufacturers, including Changchun BCHT Biotechnology and Changchun Changsheng Biotechnology Co., LTD was better than that of Varv produced by GlaxoSmithKline Biologics. There was considerable heterogeneity among the studies within each group of manufacturers, and the results need to be interpreted with caution. In addition, the imported vaccines in this study were all produced by GlaxoSmithKline Biologics in Belgium. Studies of other imported vaccines, such as those from Merck in the United States, were lacking. Future studies can also further demonstrate the differences in immunogenicity between domestic Varv and imported Varv.\u003c/p\u003e \u003cp\u003eIn our safety analysis that included 29,696 Chinese people from 25 studies, the proportion of systemic reactions to the domestic Varv was higher than that of the imported Varv; the proportion of local reactions of domestic Varv was lower than that of imported Varv. The results of subgroup analyses in different manufacturers are consistent. Our findings on local reactions are also consistent with previous studies [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. This suggests that there may be differences in the safety profiles of domestic and imported Varv vaccines in Chinese populations. Further research is needed to determine the underlying reasons for these differences and to ensure the safety and efficacy of Varv vaccines for all individuals.\u003c/p\u003e \u003cp\u003eIn short, the study found that both domestic and imported varicella vaccines are effective and safe in the Chinese population. The domestic vaccine is more affordable but may have limitations in terms of performance. The imported vaccine, while more expensive and requiring cold chain transportation, may face challenges in large-scale implementation. Overall, both vaccines have their advantages and limitations, and public health efforts should consider these factors when promoting varicella vaccination in China.\u003c/p\u003e \u003cp\u003eThe study showed that a lower proportion of systemic reactions was observed in individuals aged 13 years old or younger compared to those over 13 years old. This finding suggests that younger individuals may have a lower risk of experiencing systemic reactions following varicella vaccination compared to older individuals. This is consistent with previous findings in people living with HIV [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e]. The statement that there are fewer studies on the use of the varicella vaccine in adults compared to children highlights an important gap in current research. While varicella vaccination is commonly administered to children as part of routine immunization schedules, there is less data available on the safety and efficacy of the vaccine in adults.\u003c/p\u003e \u003cp\u003eMore studies are indeed needed in the future to demonstrate the safety and effectiveness of varicella vaccination in adults. These studies could help inform public health policies regarding the use of varicella vaccine in adult populations, especially those at higher risk of complications from varicella infection. Additionally, further research could provide valuable insights into the potential benefits of vaccinating adults against varicella, such as reducing the overall burden of varicella-related illness and complications in the population [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe also found that the proportion of local reactions with two doses of Varv was higher than with one dose. Similar results were observed in previous meta-analysis, where local reactions tended to be stronger after a second dose of varicella vaccine [\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e]. Local reactions are indeed the most common type of reactions following vaccination. These reactions typically include redness and swelling at the injection site and are generally mild and self-limited [\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e]. The higher proportion of local reactions with two doses of varicella vaccine could be due to a variety of factors, including increased immune response with the second dose or individual variability in reactions. While these reactions are typically not cause for concern, healthcare providers should be aware of this finding and monitor patients accordingly after vaccination. Previous studies have also found a lower incidence of systemic reactions (such as fever or headache) after the second dose compared to the first dose [\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e, \u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e]. Similar findings were found in this study, but were not statistically significant.\u003c/p\u003e \u003cp\u003eSeveral limitations of the present study must be acknowledged. First, the relatively small number of study on imported varicella vaccine probably leads to inaccurate evaluation of results, and also make it impossible to conduct separate subgroup analyses of domestic and imported vaccines in this study. Second, there was substantial heterogeneity in the immunogenicity and safety outcomes, which attests to important variation between the included studies. Heterogeneity did not decrease after our subgroup analyses. However, the results of sensitivity analysis showed that the immunogenicity and safety values were reliable.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, both domestically produced and imported varicella vaccines had high immunogenicity. Some differences in the types and frequencies of reactions observed. The proportion of systemic reactions was higher with domestic Varv, while the proportion of local reactions was higher with imported Varv. Overall, both domestic and imported varicella vaccines are considered safe and effective in preventing chickenpox, and individuals should follow the recommendations of healthcare providers and public health authorities regarding vaccination.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.25974025974026%\" valign=\"top\"\u003e\n \u003cp\u003eVZV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"84.74025974025975%\" valign=\"top\"\u003e\n \u003cp\u003eVaricella zoster virus\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.25974025974026%\" valign=\"top\"\u003e\n \u003cp\u003eVarV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"84.74025974025975%\" valign=\"top\"\u003e\n \u003cp\u003eLive-attenuated varicella vaccine\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.25974025974026%\" valign=\"top\"\u003e\n \u003cp\u003eCNKI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"84.74025974025975%\" valign=\"top\"\u003e\n \u003cp\u003eChina National Knowledge Internet\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.25974025974026%\" valign=\"top\"\u003e\n \u003cp\u003eSinoMed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"84.74025974025975%\" valign=\"top\"\u003e\n \u003cp\u003eChinese Biomedical Literature Service System\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.25974025974026%\" valign=\"top\"\u003e\n \u003cp\u003eNOS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"84.74025974025975%\" valign=\"top\"\u003e\n \u003cp\u003eNewcastle-Ottawa Scale\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.25974025974026%\" valign=\"top\"\u003e\n \u003cp\u003eCI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"84.74025974025975%\" valign=\"top\"\u003e\n \u003cp\u003eConfidence interval\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data set supporting this article is available on demand to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by\u0026nbsp;the\u0026nbsp;Postdoctoral\u0026nbsp;Fellowship\u0026nbsp;Program\u0026nbsp;of CPSF (Grant Number, GZB20230037), and National Social Science Fund of China (Grant Number, 21\u0026amp;ZD187).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eY.Y. and P.H. contributed to conception. Y.Y., T.W., Y.X., Z.S., and P.H. contributed to design. Y.Y. and T.W. contributed to search strategy. Y.Y., T.W., and Y.X. did study selection based on title, abstract and full text; and data extraction. Y.Y. and Z.S. contributed to data synthesis and analysis and article drafting. Y.Y. and P.H. contributed to data interpretation, article revision and review. All authors read and approved the final article.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAndrei G, Snoeck R (2021) Advances and Perspectives in the Management of Varicella-Zoster Virus Infections. Molecules 26:1132\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArvin AM (2023) Creating the Dew Drop on a Rose Petal: the Molecular Pathogenesis of Varicella-Zoster Virus Skin Lesions. 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Pediatr Infect Dis J 35:1011\u0026ndash;1020\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Peking University","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Varicella vaccine, Immunogenicity, Safety, China","lastPublishedDoi":"10.21203/rs.3.rs-5061401/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5061401/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eThis study aimed to synthesize the available evidence to compare the immunogenicity and safety of domestic and imported live-attenuated varicella vaccine (VarV) in healthy Chinese population.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003ePubMed, Web of Science, Embase, China National Knowledge Internet (CNKI), Wan Fang Database, and Chinese Biomedical Literature Service System (SinoMed) were searched using predefined search terms to identify relevant studies. The included articles reported varicella vaccine administration in healthy Chinese population. We calculated the pooled proportion of seroconversions and adverse events, and assessed the quality of each study using the modified Jadad Scale and Newcastle Ottawa Scale (NOS).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe pooled seroconversion proportion of domestic Varv was 89% (95%CI: 86%-91%) and that of imported Varv was 93% (95%CI: 88%-98%). The difference was not statistically significant. The pooled proportion of systemic reactions for domestic Varv (11%, 95%CI: 10%-13%) was higher than that of imported Varv (8%, 95%CI: 6%-10%; χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;8.04, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), but the results were opposite for local reactions (domestic Varv: 3%, 95%CI: 2%-3%; imported Varv: 7%, 95%CI: 3%-10%; χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;5.30, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.020).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eBoth domestic and imported varicella vaccines are effective and safe in the Chinese population. More evidence on imported vaccines is needed in the future to supplement our findings.\u003c/p\u003e","manuscriptTitle":"Immunogenicity and safety of the domestic and imported live-attenuated varicella vaccine in healthy Chinese population: A systematic review and meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-11 04:27:48","doi":"10.21203/rs.3.rs-5061401/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"92f13f3e-8415-458b-9f7f-bd96afe0e6a9","owner":[],"postedDate":"September 11th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-09-11T04:27:48+00:00","versionOfRecord":[],"versionCreatedAt":"2024-09-11 04:27:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5061401","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5061401","identity":"rs-5061401","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}