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基于异源加强策略的两种不同类型结核疫苗的比较免疫原性研究

Comparative immunogenicity study of two different types of tuberculosis vaccines based on a heterologous boosting strategy.

作者信息

Wang Xiaochun, Wang Runlin, Wang Jianghong, Zhang Zian, Kong LingYun, Xia Lu, Qi Zhiyang, Chen Haoying

机构信息

The First Affiliated Hospital, Anhui University of Science and Technology, Huainan, 232001, China.

Department of Pathogen Biology, School of Medicine, Anhui University of Science and Technology, Huainan, 232001, China.

出版信息

Arch Microbiol. 2025 Sep 15;207(10):262. doi: 10.1007/s00203-025-04463-4.

DOI:10.1007/s00203-025-04463-4
PMID:40952453
Abstract

BCG, one of the oldest vaccines in clinical use, has demonstrated well-documented safety, quality, and efficacy in preventing severe forms of tuberculosis (TB) in neonates. However, its protective efficacy declines significantly in adulthood, failing to prevent pulmonary the TB -a major driver of global TB transmission. To address this limitation, this study systematically evaluated two novel BCG-boosting strategies: a recombinant subunit protein vaccine targeting the Rv2074 antigen and a DNA vaccine encoding the same antigen, both evaluated in murine immunization. Antigen-specific cytokine levels in splenocyte supernatants and serum antibody titers were quantified by ELISA after euthanizing mice at 8 weeks (8w) and 16 weeks (16w) post-immunization. The results indicated that both vaccine types induced robust Th1-type immune responses in mice. Additionally, antigen-specific T cell cytokine secretion was analyzed using flow cytometry combined with intracellular cytokine staining. Experimental data revealed that the BCG + P group exhibited a significant increase in CD4 T cells, while the BCG + D group showed a higher proportion of CD8 T cells.Long-term immune effects surpassing short-term outcomes in both groups. These findings suggest that both vaccine types show promise as BCG-based booster vaccines.

摘要

卡介苗是临床使用最久的疫苗之一,在预防新生儿严重形式的结核病(TB)方面已展现出有充分记录的安全性、质量和有效性。然而,其保护效力在成年期显著下降,无法预防肺结核——全球结核病传播的主要驱动因素。为解决这一局限性,本研究系统评估了两种新型卡介苗增强策略:一种靶向Rv2074抗原的重组亚单位蛋白疫苗和一种编码相同抗原的DNA疫苗,二者均在小鼠免疫实验中进行了评估。在免疫后8周(8w)和16周(16w)对小鼠实施安乐死后,通过酶联免疫吸附测定(ELISA)对脾细胞上清液中的抗原特异性细胞因子水平和血清抗体滴度进行了定量。结果表明,两种疫苗类型均在小鼠中诱导了强烈的Th1型免疫反应。此外,使用流式细胞术结合细胞内细胞因子染色分析了抗原特异性T细胞细胞因子的分泌情况。实验数据显示,卡介苗+蛋白疫苗组的CD4 T细胞显著增加,而卡介苗+DNA疫苗组的CD8 T细胞比例更高。两组的长期免疫效果均超过短期结果。这些发现表明,两种疫苗类型作为基于卡介苗的增强疫苗均具有前景。

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本文引用的文献

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Construction and expression of Mycobacterium tuberculosis fusion protein SHR3 and its immunogenicity analysis in combination with various adjuvants.结核分枝杆菌融合蛋白SHR3的构建、表达及其与多种佐剂联合使用的免疫原性分析
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Recombinant coexpressing Ag85B-IFN-γ enhances the cell-mediated immunity in C57BL/6 mice.共表达Ag85B-IFN-γ的重组体增强C57BL/6小鼠的细胞介导免疫。
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Suppression of autophagy and antigen presentation by Mycobacterium tuberculosis PE_PGRS47.结核分枝杆菌 PE_PGRS47 对自噬和抗原呈递的抑制作用。
Nat Microbiol. 2016 Aug 15;1(9):16133. doi: 10.1038/nmicrobiol.2016.133.
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High level of IFN-γ released from whole blood of human tuberculosis infections following stimulation with Rv2073c of Mycobacterium tuberculosis.结核分枝杆菌的Rv2073c刺激后,人类结核感染全血释放出高水平的γ干扰素。
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