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一种新型嵌合重组 FliC-Pgp3 疫苗可促进对鼠型沙眼衣原体感染的免疫保护。

A novel chimeric recombinant FliC-Pgp3 vaccine promotes immunoprotection against Chlamydia muridarum infection in mice.

机构信息

Institute of Pathogenic Biology, School of Nursing, Hengyang Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province, University of South China, Hengyang 421001, Hunan, People's Republic of China.

Institute of Pathogenic Biology, School of Nursing, Hengyang Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province, University of South China, Hengyang 421001, Hunan, People's Republic of China.

出版信息

Int J Biol Macromol. 2024 Feb;258(Pt 1):128723. doi: 10.1016/j.ijbiomac.2023.128723. Epub 2023 Dec 14.

Abstract

The Pgp3 subunit vaccine elicits immune protection against Chlamydia trachomatis infection, but additional adjuvants are still required to enhance its immunoprotective efficacy. Flagellin can selectively stimulate immunity and act as an adjuvant. In this research, the FliC-Pgp3 recombinant was successfully expressed and purified. Tri-immunization with the FliC-Pgp3 vaccine in Balb/C mice induced rapid and persistent germinal center B-cell response and Tfh differentiation, promoting a significantly higher IgG antibody titer compared to the Pgp3 group. FliC-Pgp3 immunization primarily induced Th1-type cellular immunity, leading to higher levels of IFN-γ, TNF-α, and IL-2 secreted by CD4 T cells than in Pgp3-vaccinated mice. Chlamydia muridarum challenge results showed that FliC-Pgp3-vaccinated mice exhibited more rapid clearance of Chlamydia muridarum colonization in the lower genital tract, ensuring a lower hydrosalpinx rate and cumulative score. Histological analysis showed reduced dilation and inflammatory infiltration in the oviduct and uterine horn of FliC-Pgp3-vaccinated mice compared to the PBS and Pgp3 control. Importantly, tri-immunization with FliC-Pgp3 effectively activated CD4 T cells and dendritic cells, as confirmed by the adoptive transfer, resulting in better immune protection in recipient mice. In summary, the novel FliC-Pgp3 chimeric is hoped to be a novel vaccine with improved immunoprotection against Chlamydia muridarum.

摘要

Pgp3 亚单位疫苗可引发针对沙眼衣原体感染的免疫保护,但仍需要额外的佐剂来增强其免疫保护效果。鞭毛蛋白可以选择性地刺激免疫反应并作为佐剂。在这项研究中,成功表达和纯化了 FliC-Pgp3 重组蛋白。在 Balb/C 小鼠中进行三免疫接种 FliC-Pgp3 疫苗可诱导快速和持久的生发中心 B 细胞反应和 Tfh 分化,与 Pgp3 组相比,可显著提高 IgG 抗体滴度。FliC-Pgp3 免疫接种主要诱导 Th1 型细胞免疫,导致 CD4 T 细胞分泌的 IFN-γ、TNF-α 和 IL-2 水平高于 Pgp3 疫苗接种小鼠。对鼠型沙眼衣原体的攻毒结果表明,FliC-Pgp3 疫苗接种组小鼠在下生殖道更快地清除了沙眼衣原体的定植,确保了较低的输卵管积水率和累积评分。组织学分析表明,与 PBS 和 Pgp3 对照组相比,FliC-Pgp3 疫苗接种组小鼠的输卵管和子宫角扩张和炎症浸润减少。重要的是,通过过继转移证实,FliC-Pgp3 的三免疫接种有效地激活了 CD4 T 细胞和树突状细胞,从而使受体小鼠获得更好的免疫保护。总之,新型 FliC-Pgp3 嵌合蛋白有望成为一种新型疫苗,可改善对鼠型沙眼衣原体的免疫保护。

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