伤寒病毒多糖亚单位疫苗中的 TLR4 配体有助于提高免疫原性。

Q3 Medicine
Kishore R Alugupalli
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引用次数: 0

摘要

B 细胞和 T 细胞的激活除了需要 Ag 受体信号外,还需要成本刺激信号通路的参与,才能产生有效的免疫反应。伤寒病毒多糖(ViPS)亚单位疫苗都不含可激活成本调控信号通路的佐剂,但这些疫苗的免疫原性很强。我推测,用于制造伤寒亚单位疫苗的 ViPS 制剂中残留的 TLR 配体是这些疫苗产生强大免疫应答的原因。我发现在 ViPS 制剂和 ViPS 疫苗中存在内毒素,这是 TLR4 的一种强效激动剂。此外,我还发现不同来源的 ViPS 可诱导小鼠腹腔渗出液细胞产生 IL-6 等促炎细胞因子。非结合型和结合破伤风类毒素的 ViPS 疫苗可激活人类和小鼠的 TLR4。缺乏 TLR4 或信号适配体 MyD88 和 Trif(诱导 IFN-β 的含 Toll/IL-1R 域适配体)的小鼠对这些疫苗产生抗 ViPS 反应的能力严重受损。在 ViPS 制剂中去除 TLR4 激动剂会导致免疫原性丧失,而添加已知的 TLR4 激动剂脂质 A 则可恢复免疫原性。这些数据强调了相关 TLR 配体对 ViPS 亚单位疫苗免疫原性的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
TLR4 Ligands in Typhoid Vi Polysaccharide Subunit Vaccines Contribute to Immunogenicity.

Activation of B cells and T cells requires the engagement of costimulatory signaling pathways in addition to Ag receptor signaling for efficient immune responses. None of the typhoid Vi polysaccharide (ViPS) subunit vaccines contains adjuvants that could activate costimulatory signaling pathways, yet these vaccines are very immunogenic. I hypothesized that residual TLR ligands present in the ViPS preparation used for making typhoid subunit vaccines account for the robust immune response generated by these vaccines. I show the presence of endotoxin, a potent agonist of TLR4, in ViPS preparations and ViPS vaccines. Furthermore, I found that ViPS obtained from various sources induces the production of proinflammatory cytokines such as IL-6 from mouse peritoneal exudate cells. Unconjugated and tetanus toxoid-conjugated ViPS vaccines activate human and mouse TLR4. Mice deficient in TLR4 or the signaling adaptors MyD88 and Trif (Toll/IL-1R domain-containing adapter inducing IFN-β) are severely impaired in generating anti-ViPS responses to these vaccines. Elimination of the TLR4 agonist in ViPS preparation resulted in the loss of immunogenicity, and addition of lipid A, a known TLR4 agonist, restored the immunogenicity. These data highlight the importance of associated TLR ligands in the immunogenicity of ViPS subunit vaccines.

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来源期刊
CiteScore
3.70
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