Hyaluronic Acid Conjugates of TLR7/8 Agonists for Targeted Delivery to Secondary Lymphoid Tissue,Bioconjugate Chemistry

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Hyaluronic Acid Conjugates of TLR7/8 Agonists for Targeted Delivery to Secondary Lymphoid Tissue
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2018-07-03 00:00:00 , DOI: 10.1021/acs.bioconjchem.8b00386
Euna Yoo ₁ , Alex C. D. Salyer _{1,

2} , Michael J. H. Brush ₂ , Yupeng Li ₂ , Kathryn L. Trautman ₂ , Nikunj M. Shukla ₁ , Ans De Beuckelaer ₃ , Stefan Lienenklaus ₄ , Kim Deswarte ₃ , Bart N. Lambrecht ₃ , Bruno G. De Geest ₃ , Sunil A. David ₂

Affiliation

Immunogens carried in lymphatic fluid drain via afferent vessels into regional lymph nodes and facilitate the efficient induction of appropriate immune responses. The lymphatic system possesses receptors recognizing hyaluronic acid (HA). Covalent conjugates of small-molecule TLR7/8 agonists with HA are entirely devoid of immunostimulatory activity in vitro. In murine models of immunization, however, such conjugates traffic to lymph nodes, where they are “unmasked”, releasing the small molecule TLR7/8 agonist from the carrier polysaccharide. The resulting focal immunostimulation is manifested in potent adjuvantic effects with negligible systemic exposure. The efficient delivery of immunogens has been a major challenge in the development of subunit vaccines, and enhancing targeted delivery of immunogens to secondary lymphoid organs might be a promising approach for improving vaccine efficacy, as well as safety.

中文翻译：

TLR7 / 8激动剂的透明质酸缀合物可靶向递送至次级淋巴组织。

淋巴液中携带的免疫原通过传入血管排入区域淋巴结，并有助于有效诱导适当的免疫反应。淋巴系统拥有识别透明质酸（HA）的受体。小分子TLR7 / 8激动剂与HA的共价结合物在体外完全没有免疫刺激活性。但是，在鼠类免疫模型中，此类缀合物运往淋巴结，在淋巴结中“未被掩盖”，从而从载体多糖中释放出小分子TLR7 / 8激动剂。所产生的局灶性免疫刺激表现为有效的佐剂作用，而全身性暴露可忽略不计。免疫原的有效传递一直是亚单位疫苗开发的主要挑战，

更新日期：2018-07-03

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