百日咳毒力基因变异与疫苗株抗原关联性研究进展

doi:10.3877/cma.j.issn.1673-5250.2025.06.014

中华妇幼临床医学杂志(电子版) ›› 2025, Vol. 21 ›› Issue (06) : 707 -713. doi: 10.3877/cma.j.issn.1673-5250.2025.06.014

综述

百日咳毒力基因变异与疫苗株抗原关联性研究进展

余珍燕¹^,², 王启明³, 许超², 朱渝¹^,^†(

)

¹四川大学华西第二医院小儿感染科、出生缺陷与相关妇儿疾病教育部重点实验室，成都　610041
²成都市公共卫生临床医疗中心儿科，成都　610066
³成都市公共卫生临床医疗中心检验科，成都　610066

收稿日期:2025-09-18 修回日期:2025-10-29 出版日期:2025-12-01
通信作者: 朱渝

Research progress on the association between virulence gene variation of bordetella pertussis and vaccine strain antigens

Zhenyan Yu¹^,², Qiming Wang³, Chao Xu², Yu Zhu¹^,^†()

¹Department of Pediatric Infectious Diseases, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second university Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
²Department of Pediatrics, Chengdu Public Health Clinical Center, Chengdu 610066, Sichuan Province, China
³Department of Clinical Laboratory, Chengdu Public Health Clinical Center, Chengdu 610066, Sichuan Province, China

Received:2025-09-18 Revised:2025-10-29 Published:2025-12-01
Corresponding author: Yu Zhu
Supported by:
Project of Sichuan Provincial Clinical Research Center for Pediatrics(Ke Ji [2017] No.46)

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余珍燕, 王启明, 许超, 朱渝. 百日咳毒力基因变异与疫苗株抗原关联性研究进展[J/OL]. 中华妇幼临床医学杂志(电子版), 2025, 21(06): 707-713.

Zhenyan Yu, Qiming Wang, Chao Xu, Yu Zhu. Research progress on the association between virulence gene variation of bordetella pertussis and vaccine strain antigens[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2025, 21(06): 707-713.

近年，在无细胞百日咳疫苗(aP)广泛应用背景下，百日咳发病率在全球多国出现回升趋势。分子流行病学研究显示，百日咳鲍特菌(Bp)多个编码疫苗相关抗原的毒力基因发生群体性变异，并伴随优势克隆谱系更替，可能参与"百日咳再现"的发生。笔者拟就近年Bp主要疫苗相关抗原基因的变异特征，包括百日咳毒素启动子(ptxP)、百日咳毒素A亚基(ptxA)、百日咳黏附素基因(prn)、丝状血凝素基因(fhaB)及菌毛基因(fim)等进行综述，并重点分析其在我国流行株中的演化趋势及其与现行共纯化无细胞百日咳疫苗(cp-ACVs)抗原组分之间的差异。现有证据表明，疫苗免疫压力可能驱动prn表达缺失、ptxP3及ptxA1等非疫苗型等位基因的扩增，同时在抗菌药物选择压力作用下形成携带多重特征的优势克隆群。上述抗原结构改变可能增加疫苗抗原错配与免疫逃逸的潜在风险。基于此，持续开展基于全基因组测序的分子流行病学监测，并结合宿主免疫应答机制优化疫苗抗原设计，是应对Bp持续演化、提升百日咳防控效能的重要方向。

关键词: 百日咳鲍特菌, 毒力基因, Prn缺失株, 疫苗逃逸, 分子流行病学, 无细胞百日咳疫苗, 疫苗研发

In recent years, against the backdrop of widespread administration of acellular pertussis (aP) vaccines, the incidence of pertussis has exhibited a resurgent trend in numerous countries across the globe. Molecular epidemiological studies have revealed that population-level variations have occurred in multiple virulence genes encoding vaccine-associated antigens of Bordetella pertussis (Bp), accompanied by the replacement of dominant clonal lineages, which may be implicated in the phenomenon of "pertussis resurgence". This review summarizes the variation characteristics of major vaccine-associated antigen genes of Bp in recent years, including pertussis toxin promoter (ptxP), pertussis toxin subunit A (ptxA), pertactin gene (prn), filamentous hemagglutinin gene (fhaB), and fimbriae gene (fim), with a focus on the analysis of their evolutionary trends in circulating strains in China and the discrepancies from the antigen components of currently used co-purified acellular pertussis vaccines (cp-ACVs). Available evidence demonstrates that vaccine immune pressure may drive the expansion of non-vaccine-type alleles such as prn deficiency, ptxP3, and ptxA1, while antimicrobial selective pressure facilitates the formation of dominant clonal clusters harboring multiple phenotypic characteristics. The aforementioned structural alterations of antigens may elevate the potential risks of vaccine antigen mismatch and immune escape. Accordingly, sustainable implementation of whole-genome sequencing-based molecular epidemiological surveillance, combined with optimization of vaccine antigen design by integrating host immune response mechanisms, constitutes a crucial strategy to counteract the continuous evolution of Bp and enhance the efficacy of pertussis prevention and control.

Key words: Bordetella pertussis, Virulence genes, Prn-deficient strains, Vaccine escape, Molecular epidemiology, Acellular pertussis vaccines, Vaccine development

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