Article(id=1320427723886019122, tenantId=1146029695717560320, journalId=1319373219989389464, issueId=1320427658937225679, articleNumber=null, orderNo=null, doi=10.11847/zgggws1149152, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1761062400000, receivedDateStr=2025-10-22, revisedDate=1769443200000, revisedDateStr=2026-01-27, acceptedDate=1772985600000, acceptedDateStr=2026-03-09, onlineDate=1792744101734, onlineDateStr=2026-10-23, pubDate=1786291200000, pubDateStr=2026-08-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1792744101734, onlineIssueDateStr=2026-10-23, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1792744101734, creator=13701087609, updateTime=1792744101734, updator=13701087609, issue=Issue{id=1320427658937225679, tenantId=1146029695717560320, journalId=1319373219989389464, year='2026', volume='42', issue='8', pageStart='897', pageEnd='1024', issueExtLink='null', onlineDate='null', pubDate='1786291200000', pubDateStr='2026-08-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1792744086250, creator='13701087609', updateTime=1792747993375, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1320444046678544663, tenantId=1146029695717560320, journalId=1319373219989389464, issueId=1320427658937225679, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1320444046678544664, tenantId=1146029695717560320, journalId=1319373219989389464, issueId=1320427658937225679, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=999, endPage=1006, ext={EN=ArticleExt(id=1320427724087345715, articleId=1320427723886019122, tenantId=1146029695717560320, journalId=1319373219989389464, language=EN, title=Immunogenicity, antibody persistence, and safety of Japanese encephalitis vaccines in primary immunization: a meta-analysis, columnId=1320427670123430037, journalTitle=Chinese Journal of Public Health, columnName=Evidence-Based Medicine, runingTitle=null, highlight=null, articleAbstract=
Objective

To evaluate the effectiveness, antibody persistence, and safety of Japanese encephalitis (JE) attenuated live vaccines and inactivated (Vero cell) vaccines currently used in China's national immunization program following primary immunization, thus providing evidence for optimizing JE vaccination strategies in China.

Methods

We systematically searched CNKI, Wanfang Data, PubMed, Cochrane Library, and Web of Science for randomized controlled trials (RCTs) on the safety and effectiveness of JE vaccines that were published from January 1, 2000 to February 28, 2025. RevMan 5.3 and R 4.4.1 were used for single-arm proportion meta-analyses.

Results

A total of 20 eligible articles (9 in Chinese, 11 in English) were included, comprising 27 vaccine cohorts with 5 445 participants. Meta-analysis results showed that the pooled seroconversion rate (SCR) 28–30 days after primary immunization was 91.12% (95%CI: 84.75%–94.99%). The pooled antibody persistence rate 1 year after primary immunization was 86.32% (95%CI: 62.75%–95.94%). The pooled incidence of total adverse events (AEs) was 24.10% (95%CI: 14.59%–37.11%), and the pooled incidence of serious adverse events (SAEs) was 0.19% (95%CI: 0.00%–0.91%). Subgroup analyses revealed differences in SCR across different geographical regions and age groups (all P < 0.01). However, no significant differences were found in SCR, antibody persistence rate, total incidence of AEs, or incidence of SAEs between different vaccine types (all P > 0.05). Similarly, no significant differences were observed across regions or age groups for antibody persistence rate, total incidence of AEs, or incidence of SAEs (all P > 0.05). Sensitivity analysis using the study removal method showed that the meta-analysis results remained stable after excluding smaller studies.

Conclusions

The JE vaccines currently used in China demonstrate great immunogenicity, sustained immune protection, and acceptable safety after primary immunization. It is recommended that regional and population differences be considered in immunization strategy planning, and immunization protection and post-vaccination monitoring be strengthened for key populations such as children.

, authors=Jiaxin XIE1, 2, Chengbin SHI1, 2, Jiamin QIU1, 2, Zhanjie ZHAO3, Fangfang ZENG1, 2, Xiaofeng LIANG3, authorsList=Jiaxin XIE, Chengbin SHI, Jiamin QIU, Zhanjie ZHAO, Fangfang ZENG, Xiaofeng LIANG, authorCompany=null, correspAuthors=Xiaofeng LIANG, authorNote=null, correspAuthorsNote=
LIANG Xiaofeng, E-mail:
, copyrightStatement=Copyright © 2026 Chinese Journal of Public Health. All rights reserved., copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1320427724716491320, articleId=1320427723886019122, tenantId=1146029695717560320, journalId=1319373219989389464, language=CN, title=流行性乙型脑炎疫苗基础免疫有效性、持久性及安全性meta分析, columnId=1320427670287007895, journalTitle=中国公共卫生, columnName=循证医学, runingTitle=null, highlight=null, articleAbstract=
目的

评价中国现行免疫规划中使用的流行性乙型脑炎(简称“乙脑”)减毒活疫苗和灭活疫苗(Vero细胞)基础免疫后的有效性、持久性及安全性,为优化我国乙脑疫苗的免疫策略提供参考依据。

方法

检索中国知网数据库、万方数据知识服务平台、PubMed数据库、Cochrane数据库和 Web of Science 数据库,收集2000年1月1日—2025年2月28日国内外公开发表的有关乙脑疫苗安全性和有效性的随机对照试验文献,应用RevMan 5.3 和 R 4.4.1 软件对纳入的文献进行单组率meta分析。

结果

最终纳入20篇相关文献(中文文献9篇、英文文献11篇),包括27个疫苗队列人群,累计研究对象5 445人。Meta分析结果显示,乙脑疫苗基础免疫后28~30 d合并血清阳转率为91.12%(95%CI=84.75%~94.99%),基础免疫后1年合并抗体阳性率为86.32%(95%CI=62.75%~95.94%),基础免疫后总不良反应合并发生率为24.10%(95%CI=14.59%~37.11%);严重不良反应合并发生率为0.19%(95%CI=0~0.91%)。亚组分析结果显示,不同地区和年龄人群乙脑疫苗基础免疫后血清阳转率差异均有统计学意义(均P<0.01)。不同类型乙脑疫苗基础免疫后血清阳转率、抗体阳性率、总不良反应发生率和严重不良反应发生率差异均无统计学意义(均P>0.05),不同地区和年龄人群乙脑疫苗基础免疫后抗体阳性率、总不良反应发生率和严重不良反应发生率差异均无统计学意义(均P>0.05)。通过文献剔除法进行敏感性分析,结果显示,剔除较小样本的研究后,本次meta分析结果较为稳定。

结论

中国现行使用的乙脑疫苗基础免疫后表现出良好的免疫原性、持续的免疫保护及可接受的安全性,其免疫应答受接种地区和受种者年龄的显著影响。

, authors=谢佳欣1, 2, 石程宾1, 2, 邱嘉敏1, 2, 赵占杰3, 曾芳芳1, 2, 梁晓峰3, *, *, authorsList=谢佳欣, 石程宾, 邱嘉敏, 赵占杰, 曾芳芳, 梁晓峰, authorCompany=null, correspAuthors=梁晓峰, authorNote=

谢佳欣(2002—),硕士在读,研究方向:公共卫生与流行病学

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梁晓峰,E-mail:
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谢佳欣(2002—),硕士在读,研究方向:公共卫生与流行病学

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Expert review of vaccines, 2024, 23(1): 958-965., articleTitle=null, refAbstract=null), Reference(id=1320427736569594532, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=35, rfOrder=34, authorNames=null, journalName=null, refType=null, unstructuredReference=Chugh P, Soni S, Ghanghas N, et al. Comprehensive insights into Japanese encephalitis virus: From molecular characterization to advanced detection and vaccine strategies[J]. Antiviral research, 2025, 243: 106268., articleTitle=null, refAbstract=null), Reference(id=1320427736645092005, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=36, rfOrder=35, authorNames=null, journalName=null, refType=null, unstructuredReference=Zhang C, Liu Y, Luo X, et al. Real-world safety profile of live attenuated Japanese encephalitis vaccine before and after the vaccine administration law[J]. PloS one, 2025, 20(6): e0326257., articleTitle=null, refAbstract=null), Reference(id=1320427736712200870, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=37, rfOrder=36, authorNames=null, journalName=null, refType=null, unstructuredReference=World Health Organization. WHO Expert Committee on Biological Standardization: Fifty-eighth Report [M]. Geneva: WHO Press, 2008., articleTitle=null, refAbstract=null), Reference(id=1320427736796086951, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=38, rfOrder=37, authorNames=null, journalName=null, refType=null, unstructuredReference=尹遵栋, 罗会明, 李艺星, 等. 流行性乙型脑炎疫苗基础免疫血清学效果的Meta分析[J]. 中国疫苗和免疫, 2009, 15(6): 501-506., articleTitle=null, refAbstract=null), Reference(id=1320427736863195816, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=39, rfOrder=38, authorNames=null, journalName=null, refType=null, unstructuredReference=Wang S Y, Cheng X H, Li J X, et al. Comparing the immunogenicity and safety of 3 Japanese encephalitis vaccines in Asia-Pacific area: A systematic review and meta-analysis[J]. Human vaccines & immunotherapeutics, 2015, 11(6): 1418-1425., articleTitle=null, refAbstract=null), Reference(id=1320427736926110377, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=40, rfOrder=39, authorNames=null, journalName=null, refType=null, unstructuredReference=Furuya-Kanamori L, Xu C, Doi S A R, et al. Comparison of immunogenicity and safety of licensed Japanese encephalitis vaccines: A systematic review and network meta-analysis[J]. Vaccine, 2021, 39(32): 4429-4436., articleTitle=null, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1320427724959760953, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, xref=1, ext=[AuthorCompanyExt(id=1320427724968149562, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, companyId=1320427724959760953, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Preventive Medicine, School of Medicine, Jinan University/Disease Control and Prevention Institute of Jinan University/Kangtai Biological Vaccine Industry Research Institute, Jinan University, Guangzhou 510632, China), AuthorCompanyExt(id=1320427724980732475, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, companyId=1320427724959760953, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1暨南大学基础医学与公共卫生学院预防医学系/暨南大学疾病预防与控制研究院/暨南大学康泰生物疫苗产业研究院,广州 510632)]), AuthorCompany(id=1320427726507459133, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, xref=2, ext=[AuthorCompanyExt(id=1320427726515847742, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, companyId=1320427726507459133, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2Key Laboratory of Viral Pathogenesis and Prevention, Ministry of Education, Jinan University, Guangzhou 510632, China), AuthorCompanyExt(id=1320427726524236351, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, companyId=1320427726507459133, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2暨南大学病毒致病及防控教育部重点实验室,广州 510632)]), AuthorCompany(id=1320427726750728768, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, xref=3, ext=[AuthorCompanyExt(id=1320427726759117377, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, companyId=1320427726750728768, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 511430, China), AuthorCompanyExt(id=1320427726767505986, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, companyId=1320427726750728768, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3广东省疾病预防控制中心,广州 511430)])], figs=[ArticleFig(id=1320427730974392945, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, language=EN, label=Fig.1, caption=Literature screening flowchart, figureFileSmall=KR445yhQj4I9cNNXO3/6cw==, figureFileBig=gFdsNuAIlybWXGgAyEED5w==, tableContent=null), ArticleFig(id=1320427731049890418, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, language=CN, label=图1, caption=文献筛选流程图, figureFileSmall=KR445yhQj4I9cNNXO3/6cw==, figureFileBig=gFdsNuAIlybWXGgAyEED5w==, tableContent=null), ArticleFig(id=1320427731259605619, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, language=EN, label=Fig.2, caption=Risk bias diagram of included literature, figureFileSmall=JBQvXBe42Loe8VHDPoeY9Q==, figureFileBig=ZWJscxQGYQm60AgjgcK4oA==, tableContent=null), ArticleFig(id=1320427731330908788, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, language=CN, label=图2, caption=纳入文献风险偏倚图, figureFileSmall=JBQvXBe42Loe8VHDPoeY9Q==, figureFileBig=ZWJscxQGYQm60AgjgcK4oA==, tableContent=null), ArticleFig(id=1320427731393823349, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, language=EN, label=Tab.1, caption=

Basic characteristics of the literature included in meta-analysis

, figureFileSmall=null, figureFileBig=null, tableContent=
第一作者发表年份研究地区a研究对象b样本量/人使用疫苗类型接种方案c
郭绍红[15]2002中国6~17岁年长儿童组107灭活疫苗(Vero细胞)0*1,7*1
郭绍红[15]2002中国6~17岁年长儿童组123减毒活疫苗0*1
郭绍红[16]2002中国6~17岁年长儿童组105灭活疫苗(Vero细胞)0*1,7*1
郭绍红[16]2002中国6~17岁年长儿童组45减毒活疫苗0*1
张合润[17]2002中国1~5岁幼龄儿童组141减毒活疫苗0*1
殷纪牧[18]2002中国<1岁婴儿组105灭活疫苗(Vero细胞)0*1,7*1
贾丽丽[19]2003中国6~17岁年长儿童组28减毒活疫苗0*1
Kuzuhara S[20]2003其他东亚地区≥18岁成人组30灭活疫苗(Vero细胞)0*1,7~28*1
Lyons A[21]2007欧美地区≥18岁成人组24灭活疫苗(Vero细胞)0*1,28*1
李万军[22]2007中国1~5岁幼龄儿童组824减毒活疫苗0*1
李万军[22]2007中国1~5岁幼龄儿童组1 040灭活疫苗(Vero细胞)0*1,7*1
Tauber E[23]2007欧美地区≥18岁成人组419灭活疫苗(Vero细胞)0*1,28*1
李薇[24]2009中国1~5岁幼龄儿童组101灭活疫苗(Vero细胞)0*1,7*1
周荔葆[25]2009中国1~5岁幼龄儿童组187灭活疫苗(Vero细胞)0*1,7*1
Kaltenböck A[26]2010南亚及东南亚国家1~5岁幼龄儿童组24灭活疫苗(Vero细胞)0*1,28*1
张振华[27]2012中国<1岁婴儿组142减毒活疫苗0*1
张振华[27]2012中国<1岁婴儿组143灭活疫苗(Vero细胞)0*1,7*1
Feroldi E[28]2014南亚及东南亚国家<1岁婴儿组152减毒活疫苗0*1
Kim D S[29]2014其他东亚地区1~5岁幼龄儿童组137减毒活疫苗0*1
Miyazaki C[30]2014其他东亚地区1~5岁幼龄儿童组163灭活疫苗(Vero细胞)0*1,14~28*1
Miyazaki C[30]2014其他东亚地区1~5岁幼龄儿童组
Singh A[31]2015南亚及东南亚国家≥18岁成人组478灭活疫苗(Vero细胞)0*1,28*1
Singh A[31]2015南亚及东南亚国家≥18岁成人组166减毒活疫苗0*1
Yun K W[32]2015其他东亚地区1~5岁幼龄儿童组103灭活疫苗(Vero细胞)0*1,14*1
Vadrevu K M[33]2020南亚及东南亚国家6~17岁年长儿童组180灭活疫苗(Vero细胞)0*1
Vadrevu K M[33]2020南亚及东南亚国家6~17岁年长儿童组179减毒活疫苗0*1
Wang H H[34]2024中国<1岁婴儿组299灭活疫苗(Vero细胞)0*1,7*1
), ArticleFig(id=1320427731481903734, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, language=CN, label=表1, caption=

纳入meta分析文献一般特征

, figureFileSmall=null, figureFileBig=null, tableContent=
第一作者发表年份研究地区a研究对象b样本量/人使用疫苗类型接种方案c
郭绍红[15]2002中国6~17岁年长儿童组107灭活疫苗(Vero细胞)0*1,7*1
郭绍红[15]2002中国6~17岁年长儿童组123减毒活疫苗0*1
郭绍红[16]2002中国6~17岁年长儿童组105灭活疫苗(Vero细胞)0*1,7*1
郭绍红[16]2002中国6~17岁年长儿童组45减毒活疫苗0*1
张合润[17]2002中国1~5岁幼龄儿童组141减毒活疫苗0*1
殷纪牧[18]2002中国<1岁婴儿组105灭活疫苗(Vero细胞)0*1,7*1
贾丽丽[19]2003中国6~17岁年长儿童组28减毒活疫苗0*1
Kuzuhara S[20]2003其他东亚地区≥18岁成人组30灭活疫苗(Vero细胞)0*1,7~28*1
Lyons A[21]2007欧美地区≥18岁成人组24灭活疫苗(Vero细胞)0*1,28*1
李万军[22]2007中国1~5岁幼龄儿童组824减毒活疫苗0*1
李万军[22]2007中国1~5岁幼龄儿童组1 040灭活疫苗(Vero细胞)0*1,7*1
Tauber E[23]2007欧美地区≥18岁成人组419灭活疫苗(Vero细胞)0*1,28*1
李薇[24]2009中国1~5岁幼龄儿童组101灭活疫苗(Vero细胞)0*1,7*1
周荔葆[25]2009中国1~5岁幼龄儿童组187灭活疫苗(Vero细胞)0*1,7*1
Kaltenböck A[26]2010南亚及东南亚国家1~5岁幼龄儿童组24灭活疫苗(Vero细胞)0*1,28*1
张振华[27]2012中国<1岁婴儿组142减毒活疫苗0*1
张振华[27]2012中国<1岁婴儿组143灭活疫苗(Vero细胞)0*1,7*1
Feroldi E[28]2014南亚及东南亚国家<1岁婴儿组152减毒活疫苗0*1
Kim D S[29]2014其他东亚地区1~5岁幼龄儿童组137减毒活疫苗0*1
Miyazaki C[30]2014其他东亚地区1~5岁幼龄儿童组163灭活疫苗(Vero细胞)0*1,14~28*1
Miyazaki C[30]2014其他东亚地区1~5岁幼龄儿童组
Singh A[31]2015南亚及东南亚国家≥18岁成人组478灭活疫苗(Vero细胞)0*1,28*1
Singh A[31]2015南亚及东南亚国家≥18岁成人组166减毒活疫苗0*1
Yun K W[32]2015其他东亚地区1~5岁幼龄儿童组103灭活疫苗(Vero细胞)0*1,14*1
Vadrevu K M[33]2020南亚及东南亚国家6~17岁年长儿童组180灭活疫苗(Vero细胞)0*1
Vadrevu K M[33]2020南亚及东南亚国家6~17岁年长儿童组179减毒活疫苗0*1
Wang H H[34]2024中国<1岁婴儿组299灭活疫苗(Vero细胞)0*1,7*1
), ArticleFig(id=1320427731590955639, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, language=EN, label=Tab.2, caption=

Subgroup analysis of effectiveness

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特征分类文献数异质性检验结果效应模型meta分析
I2值/%Q值P值血清阳转率/%95%CI/%P值
乙脑疫苗类型减毒活疫苗1092.67122.81<0.001随机87.7671.77~95.290.068
灭活疫苗(Vero细胞)1690.16152.42<0.001随机96.2691.29~98.44
地区中国1089.17120.02<0.001随机89.1181.58~93.80<0.001
其他东亚国家 4 0.000.001.000固定99.7498.17~99.96
欧美国家 2 0.000.330.848固定97.3995.22~98.59
南亚及东南亚国家 496.98165.26<0.001随机89.5566.90~97.32
年龄/岁<1 494.87 77.90<0.001随机94.7977.77~98.960.004
1~5 872.62 32.87<0.001随机96.7487.75~99.19
6~17 595.95172.64<0.001随机84.1768.11~92.97
≥18 3 0.000.330.954固定97.5895.56~98.69
), ArticleFig(id=1320427731649675896, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, language=CN, label=表2, caption=

有效性指标的亚组分析

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特征分类文献数异质性检验结果效应模型meta分析
I2值/%Q值P值血清阳转率/%95%CI/%P值
乙脑疫苗类型减毒活疫苗1092.67122.81<0.001随机87.7671.77~95.290.068
灭活疫苗(Vero细胞)1690.16152.42<0.001随机96.2691.29~98.44
地区中国1089.17120.02<0.001随机89.1181.58~93.80<0.001
其他东亚国家 4 0.000.001.000固定99.7498.17~99.96
欧美国家 2 0.000.330.848固定97.3995.22~98.59
南亚及东南亚国家 496.98165.26<0.001随机89.5566.90~97.32
年龄/岁<1 494.87 77.90<0.001随机94.7977.77~98.960.004
1~5 872.62 32.87<0.001随机96.7487.75~99.19
6~17 595.95172.64<0.001随机84.1768.11~92.97
≥18 3 0.000.330.954固定97.5895.56~98.69
), ArticleFig(id=1320427731733561977, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, language=EN, label=Tab.3, caption=

Subgroup analysis of antibody persistence

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特征分类文献数异质性检验结果效应模型meta分析
I2值/%Q值P值抗体阳性率/%95%CI/%P值
乙脑疫苗类型减毒活疫苗396.64 59.50<0.001随机 71.7020.26~96.190.161
灭活疫苗(Vero细胞)675.03 20.02<0.001随机 97.0467.92~99.80
地区中国382.54 17.190.002随机 86.9253.15~97.500.957
其他东亚国家10.000.001.000固定100.000.00~100.00
欧美国家10.000.001.000固定100.000.00~100.00
南亚及东南亚国家297.83 76.40<0.001随机 74.6524.32~96.43
年龄/岁<1218.30 77.90<0.001随机 91.6463.08~98.600.269
1~52 0.00 32.871.000固定 94.7190.14~97.22
6~17233.89172.64<0.001随机 74.1871.18~76.97
≥1810.000.001.000固定100.000.00 ~100.00
), ArticleFig(id=1320427731809059450, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, language=CN, label=表3, caption=

持久性指标的亚组分析

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特征分类文献数异质性检验结果效应模型meta分析
I2值/%Q值P值抗体阳性率/%95%CI/%P值
乙脑疫苗类型减毒活疫苗396.64 59.50<0.001随机 71.7020.26~96.190.161
灭活疫苗(Vero细胞)675.03 20.02<0.001随机 97.0467.92~99.80
地区中国382.54 17.190.002随机 86.9253.15~97.500.957
其他东亚国家10.000.001.000固定100.000.00~100.00
欧美国家10.000.001.000固定100.000.00~100.00
南亚及东南亚国家297.83 76.40<0.001随机 74.6524.32~96.43
年龄/岁<1218.30 77.90<0.001随机 91.6463.08~98.600.269
1~52 0.00 32.871.000固定 94.7190.14~97.22
6~17233.89172.64<0.001随机 74.1871.18~76.97
≥1810.000.001.000固定100.000.00 ~100.00
), ArticleFig(id=1320427731876168315, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, language=EN, label=Tab.4, caption=

Subgroup analysis of the total incidence of adverse events

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特征分类文献数异质性检验结果效应模型meta分析
I2值/%Q值P值总不良反应率/%95%CI/%P值
乙脑疫苗类型减毒活疫苗 482.48 17.12<0.001随机24.3316.59~34.200.968
灭活疫苗(Vero细胞)1196.70302.77<0.001随机23.9711.95~42.27
地区中国 697.04236.10<0.001随机19.9810.79~32.950.345
其他东亚国家 295.76 23.61<0.001随机30.77 0.95~95.36
南亚及东南亚国家 326.815.460.360固定30.1827.44~33.06
年龄/岁<1 298.40 62.52<0.001随机42.8014.13~77.280.104
1~5 497.03134.82<0.001随机22.33 6.03~56.31
6~17 474.25 23.30<0.001随机25.6120.63~31.31
≥18 10.000.001.000固定 3.33 0.47~20.20
), ArticleFig(id=1320427731943277180, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, language=CN, label=表4, caption=

总不良反应率的亚组分析

, figureFileSmall=null, figureFileBig=null, tableContent=
特征分类文献数异质性检验结果效应模型meta分析
I2值/%Q值P值总不良反应率/%95%CI/%P值
乙脑疫苗类型减毒活疫苗 482.48 17.12<0.001随机24.3316.59~34.200.968
灭活疫苗(Vero细胞)1196.70302.77<0.001随机23.9711.95~42.27
地区中国 697.04236.10<0.001随机19.9810.79~32.950.345
其他东亚国家 295.76 23.61<0.001随机30.77 0.95~95.36
南亚及东南亚国家 326.815.460.360固定30.1827.44~33.06
年龄/岁<1 298.40 62.52<0.001随机42.8014.13~77.280.104
1~5 497.03134.82<0.001随机22.33 6.03~56.31
6~17 474.25 23.30<0.001随机25.6120.63~31.31
≥18 10.000.001.000固定 3.33 0.47~20.20
), ArticleFig(id=1320427732006191741, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, language=EN, label=Tab.5, caption=

Subgroup analysis of the incidence of serious adverse events

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特征分类文献数异质性检验结果效应模型meta分析
I2值/%Q值P值严重不良反应率/%95%CI/%P值
乙脑疫苗类型减毒活疫苗 893.90114.14<0.001随机1.140.00~4.480.118
灭活疫苗(Vero细胞)15 0.007.840.900固定0.000.00~0.01
地区中国 9 0.002.650.998固定0.000.00~0.000.055
其他东亚国家 492.58 40.43<0.001随机1.380.00~7.32
欧美国家 2 0.000.160.688固定0.000.00~0.33
南亚与东南亚国家 391.59 35.68<0.001随机1.78 0.00~11.77
年龄/岁<1 492.10 50.66<0.001随机0.760.00~4.210.904
1~5 886.45 66.43<0.001随机0.710.00~1.53
6~17 3 0.002.920.571固定0.110.00~0.66
≥18 3 0.000.260.879固定0.000.00~0.25
), ArticleFig(id=1320427732085883518, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320427723886019122, language=CN, label=表5, caption=

严重不良反应发生率的亚组分析

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特征分类文献数异质性检验结果效应模型meta分析
I2值/%Q值P值严重不良反应率/%95%CI/%P值
乙脑疫苗类型减毒活疫苗 893.90114.14<0.001随机1.140.00~4.480.118
灭活疫苗(Vero细胞)15 0.007.840.900固定0.000.00~0.01
地区中国 9 0.002.650.998固定0.000.00~0.000.055
其他东亚国家 492.58 40.43<0.001随机1.380.00~7.32
欧美国家 2 0.000.160.688固定0.000.00~0.33
南亚与东南亚国家 391.59 35.68<0.001随机1.78 0.00~11.77
年龄/岁<1 492.10 50.66<0.001随机0.760.00~4.210.904
1~5 886.45 66.43<0.001随机0.710.00~1.53
6~17 3 0.002.920.571固定0.110.00~0.66
≥18 3 0.000.260.879固定0.000.00~0.25
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流行性乙型脑炎疫苗基础免疫有效性、持久性及安全性meta分析
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谢佳欣 1, 2 , 石程宾 1, 2 , 邱嘉敏 1, 2 , 赵占杰 3 , 曾芳芳 1, 2 , 梁晓峰 3, *, *
中国公共卫生 | 循证医学 2026,42(8): 999-1006
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中国公共卫生 |循证医学 2026 , 42 (8) : 999 -1006
流行性乙型脑炎疫苗基础免疫有效性、持久性及安全性meta分析
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谢佳欣1, 2, 石程宾1, 2, 邱嘉敏1, 2, 赵占杰3, 曾芳芳1, 2, 梁晓峰3, *, *
作者信息
  • 1暨南大学基础医学与公共卫生学院预防医学系/暨南大学疾病预防与控制研究院/暨南大学康泰生物疫苗产业研究院,广州 510632
  • 2暨南大学病毒致病及防控教育部重点实验室,广州 510632
  • 3广东省疾病预防控制中心,广州 511430
通讯作者:
梁晓峰,E-mail:
作者简介:

谢佳欣(2002—),硕士在读,研究方向:公共卫生与流行病学

Immunogenicity, antibody persistence, and safety of Japanese encephalitis vaccines in primary immunization: a meta-analysis
Jiaxin XIE1, 2, Chengbin SHI1, 2, Jiamin QIU1, 2, Zhanjie ZHAO3, Fangfang ZENG1, 2, Xiaofeng LIANG3
Affiliations
  • 1Department of Preventive Medicine, School of Medicine, Jinan University/Disease Control and Prevention Institute of Jinan University/Kangtai Biological Vaccine Industry Research Institute, Jinan University, Guangzhou 510632, China
  • 2Key Laboratory of Viral Pathogenesis and Prevention, Ministry of Education, Jinan University, Guangzhou 510632, China
  • 3Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 511430, China
  • Corresponding Author:
    LIANG Xiaofeng, E-mail:
出版时间: 2026-08-10 doi: 10.11847/zgggws1149152
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目的

评价中国现行免疫规划中使用的流行性乙型脑炎(简称“乙脑”)减毒活疫苗和灭活疫苗(Vero细胞)基础免疫后的有效性、持久性及安全性,为优化我国乙脑疫苗的免疫策略提供参考依据。

方法

检索中国知网数据库、万方数据知识服务平台、PubMed数据库、Cochrane数据库和 Web of Science 数据库,收集2000年1月1日—2025年2月28日国内外公开发表的有关乙脑疫苗安全性和有效性的随机对照试验文献,应用RevMan 5.3 和 R 4.4.1 软件对纳入的文献进行单组率meta分析。

结果

最终纳入20篇相关文献(中文文献9篇、英文文献11篇),包括27个疫苗队列人群,累计研究对象5 445人。Meta分析结果显示,乙脑疫苗基础免疫后28~30 d合并血清阳转率为91.12%(95%CI=84.75%~94.99%),基础免疫后1年合并抗体阳性率为86.32%(95%CI=62.75%~95.94%),基础免疫后总不良反应合并发生率为24.10%(95%CI=14.59%~37.11%);严重不良反应合并发生率为0.19%(95%CI=0~0.91%)。亚组分析结果显示,不同地区和年龄人群乙脑疫苗基础免疫后血清阳转率差异均有统计学意义(均P<0.01)。不同类型乙脑疫苗基础免疫后血清阳转率、抗体阳性率、总不良反应发生率和严重不良反应发生率差异均无统计学意义(均P>0.05),不同地区和年龄人群乙脑疫苗基础免疫后抗体阳性率、总不良反应发生率和严重不良反应发生率差异均无统计学意义(均P>0.05)。通过文献剔除法进行敏感性分析,结果显示,剔除较小样本的研究后,本次meta分析结果较为稳定。

结论

中国现行使用的乙脑疫苗基础免疫后表现出良好的免疫原性、持续的免疫保护及可接受的安全性,其免疫应答受接种地区和受种者年龄的显著影响。

流行性乙型脑炎(乙脑)疫苗  /  基础免疫  /  血清学效果  /  短期抗体持久性  /  安全性  /  meta分析
Objective

To evaluate the effectiveness, antibody persistence, and safety of Japanese encephalitis (JE) attenuated live vaccines and inactivated (Vero cell) vaccines currently used in China's national immunization program following primary immunization, thus providing evidence for optimizing JE vaccination strategies in China.

Methods

We systematically searched CNKI, Wanfang Data, PubMed, Cochrane Library, and Web of Science for randomized controlled trials (RCTs) on the safety and effectiveness of JE vaccines that were published from January 1, 2000 to February 28, 2025. RevMan 5.3 and R 4.4.1 were used for single-arm proportion meta-analyses.

Results

A total of 20 eligible articles (9 in Chinese, 11 in English) were included, comprising 27 vaccine cohorts with 5 445 participants. Meta-analysis results showed that the pooled seroconversion rate (SCR) 28–30 days after primary immunization was 91.12% (95%CI: 84.75%–94.99%). The pooled antibody persistence rate 1 year after primary immunization was 86.32% (95%CI: 62.75%–95.94%). The pooled incidence of total adverse events (AEs) was 24.10% (95%CI: 14.59%–37.11%), and the pooled incidence of serious adverse events (SAEs) was 0.19% (95%CI: 0.00%–0.91%). Subgroup analyses revealed differences in SCR across different geographical regions and age groups (all P < 0.01). However, no significant differences were found in SCR, antibody persistence rate, total incidence of AEs, or incidence of SAEs between different vaccine types (all P > 0.05). Similarly, no significant differences were observed across regions or age groups for antibody persistence rate, total incidence of AEs, or incidence of SAEs (all P > 0.05). Sensitivity analysis using the study removal method showed that the meta-analysis results remained stable after excluding smaller studies.

Conclusions

The JE vaccines currently used in China demonstrate great immunogenicity, sustained immune protection, and acceptable safety after primary immunization. It is recommended that regional and population differences be considered in immunization strategy planning, and immunization protection and post-vaccination monitoring be strengthened for key populations such as children.

Japanese encephalitis vaccine  /  primary immunization  /  serological response  /  short-term antibody persistence  /  safety  /  meta-analysis
谢佳欣, 石程宾, 邱嘉敏, 赵占杰, 曾芳芳, 梁晓峰. 流行性乙型脑炎疫苗基础免疫有效性、持久性及安全性meta分析. 中国公共卫生, 2026 , 42 (8) : 999 -1006 . DOI: 10.11847/zgggws1149152
Jiaxin XIE, Chengbin SHI, Jiamin QIU, Zhanjie ZHAO, Fangfang ZENG, Xiaofeng LIANG. Immunogenicity, antibody persistence, and safety of Japanese encephalitis vaccines in primary immunization: a meta-analysis[J]. Chinese Journal of Public Health, 2026 , 42 (8) : 999 -1006 . DOI: 10.11847/zgggws1149152
流行性乙型脑炎(简称“乙脑”)是由三带喙库蚊传播的病毒性人兽共患病,具有高死亡率与致残率[1]。研究表明,全球每年约发生10万例乙脑临床病例并导致2.5万例死亡[2],目前尚无特效治疗方法,而接种疫苗是预防该病最经济有效的措施[3–4]。中国自2008年将乙脑疫苗纳入国家免疫规划以来,在综合防控措施的推进下,报告发病数显著下降,至2024年已降至127例[5]。一项覆盖1974—2024年共50年的模型研究表明,疫苗接种在全国范围内避免了约210万例发病、3.2万例死亡和298.9万伤残调整寿命年损失[6],充分体现了其重要的公共卫生价值。目前,我国广泛使用的乙脑疫苗主要包括乙脑减毒活疫苗和灭活疫苗(Vero细胞),两者在免疫应答、抗体持久性及安全性方面各有特点,已成为免疫规划的核心产品[7]。然而,尽管已有若干随机对照试验对其安全性与有效性进行评估,但单个研究样本量有限,结论的可靠性尚需综合论证。为评价中国现行免疫规划中使用的乙脑减毒活疫苗和灭活疫苗(Vero细胞)基础免疫后的有效性、持久性及安全性,为优化我国乙脑疫苗的免疫策略提供参考依据,本研究通过检索中国知网数据库、万方数据知识服务平台、PubMed数据库、Cochrane数据库和 Web of Science 数据库,收集2000年1月1日—2025年2月28日国内外公开发表的有关乙脑疫苗安全性和有效性的随机对照试验文献,应用RevMan 5.3 和 R 4.4.1 软件对纳入的文献进行单组率meta分析。
在中国知网数据库、万方数据知识服务平台、PubMed数据库、Cochrane 数据库和Web of Science数据库中检索2000年1月1日—2025年2月28日国内外公开发表的有关乙脑疫苗安全性和有效性的随机对照试验中、英文文献,末次检索日期为2025年3月1日。检索采用主题词与自由词相结合的策略,并根据各数据库特点进行调整,中文和英文检索词分别为“乙型/日本脑炎”“脑炎”“疫苗”“血清转化”“安全性”“随机对照试验”和“Japanese encephalitis”“brain inflammation”“Vaccines”“lmmunogenicity”“safety”“randomized controlled trial”等。同时辅以手工检索和检索纳入研究的参考文献,以补充获取相关资料。
(1)在人体中进行的比较免疫原性(即基础免疫接种后血清转化)的随机对照试验和安全性特征(即不良事件和严重不良事件);(2)疫苗类型为乙脑减毒活疫苗和灭活疫苗(Vero细胞);(3)结局指标包括:有效性(接种疫苗后28~30 d血清阳转率)、持久性(接种疫苗后1年抗体阳性率)和安全性(包括总不良反应发生率和严重不良反应发生率),研究中需采用50%空斑减少中和试验测定乙脑病毒中和抗体滴度,血清中和抗体效价≥1:10判定为阳性,免疫前抗体滴度≤1:5且免疫后抗体滴度≥1:10或免疫后抗体滴度较免疫前增长≥4倍视为发生血清转化[8]。
(1)同一研究人群、不同作者重复发表或一稿多投的文献;(2)有伴随疫苗接种或研究联合疫苗作用的研究;(3)使用除乙脑减毒活疫苗和灭活疫苗(Vero细胞)外的其他疫苗;(4)抗体滴度检测未采用50%空斑减少中和试验;(5)接种对象为动物的研究;(6)特殊人群(如牛痘患者)的研究;(7)综述、讲座、评论类文献。
收集文献资料,内容包括第一作者、发表年份、研究地区、研究对象、样本量、使用疫苗类型和接种方案等。由2名研究人员分别对每篇文献质量进行评估,当2人对同篇文献意见存在分歧时,通过咨询第3名研究人员的方式共同讨论,并最终裁定是否纳入[9]。采用Cochrane系统评价员手册5.1.0的质量评价标准推荐的随机对照试验偏倚风险评估工具对纳入的文献进行质量评价[10]。包括随机序列生成、分配隐藏、对受试者及研究人员设盲、对结局评估者设盲、不完整的结局数据、选择性报告和其他偏倚7个条目;每个条目采用低偏倚、偏倚风险不确定和高偏倚对研究质量进行判断和划分[11]。
应用RevMan 5.3和 R 4.4.1软件进行基于随机效应模型的单组率meta分析。鉴于安慰剂组无法产生特异性免疫应答且乙脑发病率极低,本研究设定的结局指标包括有效性、持久性和安全性3个指标,所有效应值均以率及其95%CI表示。研究间异质性采用I2值和Q检验评估,当I2>50%且Q检验的P<0.05时提示存在异质性,采用随机效应模型,反之则采用固定效应模型[12]。为探讨潜在的异质性来源,本研究预先设定了基于疫苗种类、地区和年龄的亚组分析,其中地区的划分参照世界卫生组织区域标准[13],并结合纳入研究的具体分布进行调整,将日本、韩国等归为其他东亚国家,将美国、德国、奥地利等归为欧美国家,将印度、泰国等归为南亚及东南亚国家,与中国共同构成4个地区亚组[14]。本研究通过剔除样本量位于后25%位的研究进行敏感性分析以评估结果稳健性,但由于单组率meta分析属描述性研究性质,其结果不存在方向性,故未进行发表偏倚检验。
共检索到2 867篇中、英文文献,阅读摘要和全文后最终纳入20篇文献(中文文献9篇、英文文献11篇),涉及27个疫苗队列人群的20项原始研究,覆盖中国、日本、美国、印度等多个国家,累计研究对象5 445人。采用Cochrane偏倚风险评估工具对纳入的20项研究进行评价。结果显示,纳入研究在多个核心领域的偏倚风险较低,在对受试者/研究人员和结局评估者盲法的实施方面有较多研究因报告不清而被判定为“偏倚风险不明”;明确的“高偏倚风险”研究较少,仅在分配隐藏、对受试者及研究人员设盲、对结局评估者设盲、不完整的结局数据等方面。
对纳入的20篇文献[15–34]进行异质性检验,文献间存在显著的异质性(I2=93.81%,P<0.001),故采用随机效应模型;meta分析结果显示,乙脑疫苗基础免疫后28~30 d合并血清阳转率为91.12%(95%CI=84.75%~94.99%)。亚组分析结果显示,中国、其他东亚国家、欧美国家和南亚及东南亚国家人群乙脑疫苗基础免疫后血清阳转率分别为89.11%、99.74%、97.39%和89.55%;<1岁、1~5岁、6~17岁和≥18岁人群乙脑疫苗基础免疫后血清阳转率分别为94.79%、96.74%、84.17%和97.58%;不同地区和年龄人群乙脑疫苗基础免疫后血清阳转率差异均有统计学意义(均P<0.01);乙脑减毒活疫苗和灭活疫苗(Vero细胞)基础免疫后血清阳转率分别为87.76%和96.26%,不同类型乙脑疫苗基础免疫后血清阳转率差异无统计学意义(P=0.068)。
对纳入的7篇文献[15–16, 21, 28, 32–34]进行异质性检验,文献间存在显著的异质性(I2=94.99%,P<0.001),故采用随机效应模型。meta分析结果显示,乙脑疫苗基础免疫后1年合并抗体阳性率为86.32%(95%CI=62.75%~95.94%)。亚组分析结果显示,乙脑减毒活疫苗和灭活疫苗(Vero细胞)基础免疫后抗体阳性率分别为71.70%和97.04%;中国、其他东亚国家、欧美国家和南亚及东南亚国家人群乙脑疫苗基础免疫后抗体阳性率分别为86.92%、100.00%、100.00%和74.65%。<1岁、1~5岁、6~17岁和≥18岁人群乙脑疫苗基础免疫后抗体阳性率分别为91.64%、94.71%、74.18%和100.00%。不同类型乙脑疫苗、地区和年龄人群乙脑疫苗基础免疫后抗体阳性率差异均无统计学意义(均P>0.05)。
对纳入的11篇文献[15–16, 18, 20, 24–26, 31–34]进行异质性检验,文献间存在显著的异质性(I2=95.76%,P<0.001),故采用随机效应模型。meta分析结果显示,乙脑疫苗基础免疫后总不良反应合并发生率为24.10%(95%CI=14.59%~37.11%)。亚组分析结果显示,乙脑减毒活疫苗和灭活疫苗(Vero细胞)基础免疫后总不良反应合并发生率分别为24.33%和23.97%。中国、其他东亚国家和南亚及东南亚国家人群乙脑疫苗基础免疫后总不良反应合并发生率分别为19.98%、30.77%和30.18%。<1岁、1~5岁、6~17岁和≥18岁人群乙脑疫苗基础免疫后总不良反应合并发生率分别为42.80%、22.33%、25.61%和3.33%。不同类型乙脑疫苗、地区和年龄人群乙脑疫苗基础免疫后总不良反应合并发生率差异均无统计学意义(均P>0.05)。
对纳入的18篇文献[15–18, 20–30, 32–34]进行异质性检验,文献间存在显著的异质性(I2=82.76%,P<0.001),故采用随机效应模型。meta分析结果显示,乙脑疫苗基础免疫后严重不良反应合并发生率为0.19%(95%CI=0~0.91%)。亚组分析结果显示,乙脑减毒活疫苗和灭活疫苗(Vero细胞)基础免疫后严重不良反应合并发生率分别为1.14%和0,中国、其他东亚国家、欧美国家和南亚及东南亚国家人群乙脑疫苗基础免疫后严重不良反应合并发生率分别为0、1.38%、0和1.78%。<1岁、1~5岁、6~17岁和≥18岁人群乙脑疫苗基础免疫后严重不良反应合并发生率分别为0.76%、0.71%、0.11%和0。不同类型乙脑疫苗、地区和年龄人群乙脑疫苗基础免疫后严重不良反应合并发生率差异均无统计学意义(均P>0.05)。
本研究通过剔除样本量位于后25%位的研究进行敏感性分析结果显示,乙脑疫苗基础免疫后28~30 d合并血清阳转率为89.44%(95%CI=79.42%~94.89%),基础免疫后1年合并抗体阳性率为81.01%(95%CI=39.76%~95.94%),基础免疫后总不良反应合并发生率为29.24%(95%CI=16.63%~46.12%),基础免疫后严重不良反应合并发生率为0.39%(95%CI=0.00%~1.41%),剔除小样本研究后本次meta分析结果保持稳定。
乙脑是一种由乙脑病毒引起的严重中枢神经系统传染病,其发病率和死亡率较高,对亚洲和西太平洋等流行地区造成了较高的疾病负担[35]。尽管目前尚无特效抗病毒药物,但疫苗接种已被证实是预防乙脑的最有效手段[4, 36]。本研究纳入20项随机对照试验进行的meta分析结果显示,乙脑疫苗基础免疫后28~30 d合并血清阳转率为91.12%(95%CI=84.75%~94.99%),表明乙脑疫苗在基础免疫阶段具有较高的免疫原性。这一结果与全球主要疫苗的预期性能一致,世界卫生组织立场文件指出,标准2剂免疫方案在第35 d的血清阳转率接近100%[7]。此外,针对中国学龄儿童的临床观察亦证实,基于北京–3株的乙脑Vero细胞灭活疫苗血清阳转率达92%[37]。亚组分析结果显示,地区和年龄是关键的异质性来源。不同地区中,欧美及其他东亚国家呈现出极高且一致的血清阳转率,表明疫苗在这些地区的免疫效果稳定。相比之下,中国、南亚及东南亚国家不仅血清阳转率相对较低,其研究间异质性也较高,提示除宏观地域差异外,可能存在当地流行的病毒亚型、基础免疫策略或流行病学背景等未知因素的共同影响。不同年龄中,≥18岁成人组的血清阳转率(97.58%)显著优于其他儿童亚组(P=0.004),反映了年龄相关的免疫系统成熟度可能对疫苗应答产生重要影响。
本研究meta分析结果还显示,乙脑疫苗基础免疫后1年合并抗体阳性率为86.32%(95%CI=62.75%~95.94%),与尹遵栋等[38]研究结果一致,提示尽管基础免疫能够迅速诱导高水平的抗体反应,但抗体的持久性仍需进一步关注。在亚组分析中,由于多数亚组纳入的文献数量较少,导致估计值的不确定性较大。因此,当前数据尚不足以得出关于乙脑疫苗类型、地区和年龄对持久性影响的明确结论,未来需要更多高质量、长期随访的研究来提供可靠证据。
在安全性方面,本研究对乙脑疫苗接种后的不良反应进行了详细评估。结果显示,乙脑疫苗基础免疫后总不良反应合并发生率为24.10%(95%CI=14.59%~37.11%),严重不良反应合并发生率为0.19%(95%CI=0~0.91%),与另一项系统评价报告中<0.1%的严重不良事件率共同印证了其优异的安全性[39]。亚组分析结果显示,严重不良事件的发生率在所有亚组中均极低,且在不同疫苗类型、地区和年龄组间差异无统计学意义,这从多个维度证实了乙脑疫苗总体安全性良好,与Furuya-Kanamori L等[40]的研究结果一致。
综上所述,乙脑疫苗在基础免疫后表现出良好的有效性,但抗体反应的持久性仍需更多长期随访研究予以确认。在安全性方面,乙脑疫苗展现出令人满意的安全性能,严重不良事件发生率极低。但本研究仍存在一定的局限性:首先,纳入的研究中不同疫苗类型及地区的分布不均衡,且部分亚组因样本量较少而导致估计结果的不确定性较大。虽然已通过统计模型对关键混杂因素进行了调整,但上述结论仍需更多高质量、设计严谨的研究加以验证,尤其是在代表性不足的地区和年龄组中;其次,本研究中抗体持久性数据仅基于1年随访,未能评估疫苗的长期保护效果。未来需进一步开展持续多年的随访研究,以明确疫苗的长期免疫持久性。

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2026年第42卷第8期
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doi: 10.11847/zgggws1149152
  • 接收时间:2025-10-22
  • 首发时间:2026-10-23
  • 出版时间:2026-08-10
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  • 收稿日期:2025-10-22
  • 修回日期:2026-01-27
  • 录用日期:2026-03-09
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    1暨南大学基础医学与公共卫生学院预防医学系/暨南大学疾病预防与控制研究院/暨南大学康泰生物疫苗产业研究院,广州 510632
    2暨南大学病毒致病及防控教育部重点实验室,广州 510632
    3广东省疾病预防控制中心,广州 511430

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