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目的 本研究旨在探索人乳头瘤病毒16型C3亚系（Human papillomavirus type 16,HPV16）主要衣壳蛋白L1对假病毒感染力及疫苗中和能力的影响。方法 通过NCBI数据库获取HPV16的16种亚系的L1蛋白序列，利用293FT细胞制备假病毒，研究C3亚系L1对上皮细胞感染能力及对希瑞适、佳达修和佳达修-9(Cervarix、Gardasil和Gardasil-9)三种疫苗敏感性之间的差异。结果 多序列比对表明C3亚系与参考蛋白（WT,P03101）相比有8个氨基酸突变位点（占比1.6%），是所有亚系中突变位点最多的。C3亚系与WT在假病毒形态、组装效率及对293FT细胞的感染能力上均无显著差异（P > 0.05）。假病毒中和试验结果显示，三种疫苗对C3亚系的中和效价较WT均显著下降。Cervarix、Gardasil和Gardasil-9对C3的中和能力分别为WT的40%、46%和50%。结论 本研究成功鉴定对当前疫苗敏感性显著性降低的C3亚系L1。它对上皮细胞感染能力不变，但是对疫苗敏感性显著降低，提示我们应该加强对不同HPV16亚系或变异体的监测，同时也为新疫苗研发提供数据支持。
Abstract：Objective This study evaluates the influence of the Human Papillomavirus type 16(HPV16) C3 sublineage L1 on pseudovirus infectivity and its susceptibility to vaccine-mediated neutralization. Methods The L1 protein sequences of 16 sublineages of HPV16 were retrieved from the NCBI database. Pseudoviruses were produced using 293 FT cells to investigate the infectivity of the C3 sublineages L1 on epithelial cell, as well as its sensitivity to three commercial vaccines(Cervarix, Gardasil, and Gardasil-9). Results Multiple sequence alignment results revealed that the C3 sublineage exhibited eight mutation sites(1.6%) compared to the reference protein(WT, P03101), making it the greatest divergence from WT among all examined sublineages. No significant differences were observed between the C3 and WT regarding pseudovirus morphology, assembly efficiency, and infection ability against 293 FT cells(P>0.05). However, pseudovirusbased neutralization assays(PBNA) revealed a significant reduction in the neutralization titers of all three vaccines against the C3 sublineage compared to WT. The neutralizing capacities of Cervarix, Gardasil, and Gardasil-9 against the C3 dropped to 40%, 46%, and 50% of the WT levels, respectively. Conclusion This study has successfully identified that the HPV16 C3 sublineage L1 significantly reduced sensitivity to current vaccines. While maintaining unchanged infectivity in epithelial cells, the C3 sublineage showed significantly decreased vaccine sensitivity, suggesting the need for strengthened surveillance of diverse HPV16 sublineages or variants. These findings also provide vital data to support the development of next-generation HPV vaccines.
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基本信息:
DOI：10.13242/j.cnki.bingduxuebao.260032
中图分类号:R373
引用信息:
[1]于东渤,卢学新,李颖,等.人乳头瘤病毒16型C3亚系L1蛋白对假病毒感染力及疫苗中和能力的影响研究[J].病毒学报,2026,42(02):436-443.DOI:10.13242/j.cnki.bingduxuebao.260032.
基金信息:
传染病溯源预警与智能决策全国重点实验室项目能力建设（项目号：ZDGWNLJS25-37）,题目：未知及新发病原体监测及预测预警技术研究; 中国疾病预防控制中心青年科学基金项目（项目号：2025A103）,题目：基于抗体与记忆B细胞的HPV疫苗免疫应答精准评估体系构建与应用研究~~
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