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首页> 外文期刊>Advanced Functional Materials >Codelivery of NOD2 and TLR9 Ligands via Nanoengineered Protein Antigen Particles for Improving and Tuning Immune Responses
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Codelivery of NOD2 and TLR9 Ligands via Nanoengineered Protein Antigen Particles for Improving and Tuning Immune Responses

机译：通过纳米工程蛋白抗原颗粒的NOD2和TLR9配体的代码传递，以改善和调节免疫反应。

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摘要

Vaccine adjuvants that can induce robust protective immunity are highly sought after for the development of safer and more effective vaccines. Vaccine formulation parameters that govern efficacy are still far from clear, such as the diverse impacts of codelivering agonist molecules for innate cell receptors (e.g., pattern recognition receptors). In this study, a mesoporous silica-templating approach is used to fabricate protein antigen (ovalbumin) particles covalently functionalized with agonists for NOD-like receptor 2 (NOD2) and Toll-like receptor 9 (TLR9). Particle-induced combinatorial NOD2/TLR9 signaling results in synergistic inflammatory cytokine secretion by mouse macrophages (RAW 264.7). Administration of NOD2/TLR9 particles in mice results in adaptive immune responses that are both quantitatively and qualitatively different than those resulting from administration of particles conjugated with either NOD2 or TLR9 agonists alone. While delivery of NOD2 agonists alone activates T helper 2 (Th2)-type responses (and no CD8+ T cell activation) and delivery of TLR9 agonists alone activates CD8+ T cell and T helper 1 (Th1)-type responses, codelivery of NOD2 and TLR9 agonists enhances Th1-type responses and abrogates CD8+ T cell activation. The results illustrate that in the particle-based system, NOD2 activation plays different roles in polarizing adaptive immune responses depending on coactivation of TLR9.
机译：为了开发更安全，更有效的疫苗，人们强烈寻求可以诱导强大的保护性免疫力的疫苗佐剂。控制效力的疫苗制剂参数还很不清楚，例如编码传递激动剂分子对先天细胞受体（例如，模式识别受体）的不同影响。在这项研究中，使用介孔二氧化硅模板方法来制备蛋白抗原（卵清蛋白）颗粒，这些颗粒与针对NOD样受体2（NOD2）和Toll样受体9（TLR9）的激动剂共价功能化。粒子诱导的组合NOD2 / TLR9信号转导导致小鼠巨噬细胞协同分泌炎症性细胞因子（RAW 264.7）。在小鼠中施用NOD2 / TLR9颗粒所产生的适应性免疫反应与单独施用与NOD2或TLR9激动剂缀合的颗粒所产生的适应性免疫反应在数量和质量上都不同。虽然单独递送NOD2激动剂会激活T辅助2（Th2）型应答（并且没有CD8 + T细胞活化），而单独递送TLR9激动剂会激活CD8 + T细胞和T辅助1（Th1）型应答，NOD2和TLR9的代码递送激动剂可增强Th1型反应并消除CD8 + T细胞活化。结果表明，在基于颗粒的系统中，取决于TLR9的共激活，NOD2激活在极化适应性免疫反应中起着不同的作用。

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  • 来源
    《Advanced Functional Materials》 |2016年第41期|7526-7536|共11页
  • 作者

    Gause Katelyn T.; Yan Yan; OBrien-Simpson Neil M.; Cui Jiwei; Lenzo Jason C.; Reynolds Eric C.; Caruso Frank;

  • 作者单位

    Univ Melbourne, ARC Ctr Excellence Convergent Bionano Sci & Techn, Parkville, Vic 3010, Australia|Univ Melbourne, Dept Chem & Biomol Engn, Parkville, Vic 3010, Australia;

    Univ Melbourne, ARC Ctr Excellence Convergent Bionano Sci & Techn, Parkville, Vic 3010, Australia|Univ Melbourne, Dept Chem & Biomol Engn, Parkville, Vic 3010, Australia|Univ Coll Dublin, Ctr BioNano Interact, Dublin 4, Ireland;

    Univ Melbourne, Melbourne Dent Sch, Oral Hlth CRC, Parkville, Vic 3010, Australia;

    Univ Melbourne, ARC Ctr Excellence Convergent Bionano Sci & Techn, Parkville, Vic 3010, Australia|Univ Melbourne, Dept Chem & Biomol Engn, Parkville, Vic 3010, Australia;

    Univ Melbourne, Melbourne Dent Sch, Oral Hlth CRC, Parkville, Vic 3010, Australia;

    Univ Melbourne, Melbourne Dent Sch, Oral Hlth CRC, Parkville, Vic 3010, Australia;

    Univ Melbourne, ARC Ctr Excellence Convergent Bionano Sci & Techn, Parkville, Vic 3010, Australia|Univ Melbourne, Dept Chem & Biomol Engn, Parkville, Vic 3010, Australia;

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