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

doi:10.21203/rs.3.rs-5061401/v1

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Systematic Review

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

https://doi.org/10.21203/rs.3.rs-5061401/v1

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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%; χ² = 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%; χ² = 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

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.

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 I² 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.

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 (I² = 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 (χ² = 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 (χ² = 0.59, P = 0.440) and non-susceptible populations (χ² = 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 (I² = 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 (χ² = 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 (I² = 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 (χ² = 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)	I² (%)	Heterogeneity (χ²)	P value	Interaction test (χ²)	P value
Age	≤ 13	26	7,027	90 (88–92)	95.90	609.54	< 0.001	0.72	0.400
	> 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. ^aOther 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)	I² (%)	Heterogeneity (χ²)	P value	Interaction test (χ²)	P value
Systemic reactions
Age	≤ 13	36	28,381	10 (9–12)	98.39	2171.87	< 0.001	61.77	< 0.001
	> 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	< 0.001	1.33	0.250
	> 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. ^aOther 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.

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.

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.

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

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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Table 1 is available in the Supplementary Files section.

The authors declare no competing interests.

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

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Immunogenicity of domestic Varv and imported Varv

Safety of domestic Varv and imported Varv

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