关键词: Adjuvant Chlamydia muridarum Flagellin Immunoprotection Pgp3

Mesh : Animals Mice Bacterial Proteins Antigens, Bacterial Chlamydia muridarum Chlamydia Infections / pathology prevention & control Immunization Vaccines, Synthetic Adjuvants, Immunologic

来  源:   DOI:10.1016/j.ijbiomac.2023.128723

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功效。鞭毛蛋白可以选择性地刺激免疫并充当佐剂。在这项研究中,成功表达并纯化了FliC-Pgp3重组体。用FliC-Pgp3疫苗在Balb/C小鼠中进行三免疫诱导快速和持续的生发中心B细胞反应和Tfh分化,促进显著高于Pgp3组的IgG抗体滴度。FliC-Pgp3免疫主要诱导Th1型细胞免疫,导致更高水平的IFN-γ,TNF-α,和IL-2分泌的CD4+T细胞比接种Pgp3的小鼠。鼠衣原体攻击结果表明,FliC-Pgp3疫苗接种的小鼠在下生殖道中表现出更快的清除鼠衣原体定植,确保较低的输卵管积水率和累积评分。组织学分析显示,与PBS和Pgp3对照相比,FliC-Pgp3接种的小鼠的输卵管和子宫角中的扩张和炎性浸润减少。重要的是,FliC-Pgp3三免疫有效激活CD4+T细胞和树突状细胞,正如收养转移所证实的那样,导致受体小鼠更好的免疫保护。总之,新型FliC-Pgp3嵌合蛋白有望成为一种新型疫苗,具有改善的抗鼠衣原体免疫保护作用.
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