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Nature子刊:武汉病毒所在重组鞭毛素粘膜佐剂和龋齿粘膜疫苗研究成果

摘要 : 粘膜是人体呼吸道、消化道、泌尿生殖道与外界沟通的门户,也是细菌、病毒等各种感染性病原入侵的主要途径。

 粘膜是人体呼吸道、消化道、泌尿生殖道与外界沟通的门户,也是细菌、病毒等各种感染性病原入侵的主要途径。利用粘膜这一特性,开发粘膜佐剂,在其辅助下,使疫苗在粘膜部位诱导产生免疫应答,能够阻断病原体的侵入渠道从而防止感染。

武汉病毒所粘膜免疫学科组经过多年不懈努力在重组鞭毛素粘膜佐剂和龋齿粘膜疫苗研究方面取得系列成果。最近,该学科组在龋齿粘膜疫苗研究方面的最新研究进展,文章以“Activation of NLRC4 downregulates TLR5-mediated antibody immune responses against flagellin”为题发到Nature旗下Cellular & Molecular Immunology,同时以题目“Flagellin-PAc Fusion Protein Inhibits Progression of Established Caries”近期正式发表在Journal of Dental Research(July 2015, Vol. 94)上,“龋齿疫苗及其制备方法”发明专利亦于近期通过了美国专利和商标局审查,即将正式授权。

粘膜免疫特异性效应因子--分泌型IgA抗体是发挥粘膜第一道防线功能的关键,能有效提高粘膜特异性防御病原入侵的能力。该学科组采用融合蛋白表达技术,将鞭毛素蛋白佐剂和龋齿疫苗抗原PAc融合表达为一个既包含粘膜佐剂又包含疫苗目标抗原的重组蛋白(KF-rPAc),以增强疫苗的保护效果。结果证明KF-rPAc融合蛋白对于已发生龋患的大鼠能诱导产生高滴度的特异性血清和唾液抗体应答,并显著抑制已发龋坏的恶化。该研究结果提示对已发龋患的个体进行有效的粘膜疫苗免疫能够延缓甚至终止龋患的进展,KF-rPAc融合蛋白也具有治疗性龋齿疫苗的功能,能适用于更广泛的临床需求。

原文链接:

Activation of NLRC4 downregulates TLR5-mediated antibody immune responses against flagellin

原文摘要:

Bacterial flagellin is a unique pathogen-associated molecular pattern (PAMP), which can be recognized by surface localized Toll-like receptor 5 (TLR5) and the cytosolic NOD-like receptor (NLR) protein 4 (NLRC4) receptors. Activation of the TLR5 and/or NLRC4 signaling pathways by flagellin and the resulting immune responses play important roles in anti-bacterial immunity. However, it remains unclear how the dual activities of flagellin that activate the TLR5 and/or NLRC4 signaling pathways orchestrate the immune responses. In this study, we assessed the effects of flagellin and its mutants lacking the ability to activate TLR5 and NLRC4 alone or in combination on the adaptive immune responses against flagellin. Flagellin that was unable to activate NLRC4 induced a significantly higher antibody response than did wild-type flagellin. The increased antibody response could be eliminated when macrophages were depleted in vivo. The activation of NLRC4 by flagellin downregulated the flagellin-induced and TLR5-mediated immune responses against flagellin.

来源: Cellular & Molecular Immunolog 浏览次数:0

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