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首页> 外文期刊>Science Immunology >A particulate saponin/TLR agonist vaccine adjuvant alters lymph flow and modulates adaptive immunity
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A particulate saponin/TLR agonist vaccine adjuvant alters lymph flow and modulates adaptive immunity

机译:颗粒状皂苷/TLR激动剂疫苗辅助改变淋巴流量并调节适应性免疫

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摘要

Saponins are potent and safe vaccine adjuvants, but their mechanisms of action remain incompletely understood. Here, we explored the properties of several saponin formulations, including immune-stimulatory complexes (ISCOMs) formed by the self-assembly of saponin and phospholipids in the absence or presence of the Toll-like receptor 4 agonist monophosphoryl lipid A (MPLA). We found that MPLA self-assembles with saponins to form particles physically resembling ISCOMs, which we termed saponin/MPLA nanoparticles (SMNP). Saponin-containing adjuvants exhibited distinctive mechanisms of action, altering lymph flow in a mast cell–dependent manner and promoting antigen entry into draining lymph nodes. SMNP was particularly effective, exhibiting even greater potency than the compositionally related adjuvant AS01B in mice, and primed robust germinal center B cell, TFH, and HIV tier 2 neutralizing antibodies in nonhuman primates. Together, these findings shed new light on mechanisms by which saponin adjuvants act to promote the immune response and suggest that SMNP may be a promising adjuvant in the setting of HIV, SARS-CoV-2, and other pathogens.
机译:皂苷是有效且安全的疫苗佐剂,但它们的作用机理仍然不完全理解。在这里,我们探索了几种皂苷配方的特性,包括在不存在或存在类似收费的受体单磷酸脂质脂质A(MPLA)的情况下,由皂苷和磷脂自组装形成的免疫刺激复合物(ISCOMS)。我们发现MPLA与皂苷的自组装形成了物理上类似于ISCOM的粒子,我们称其为皂苷/MPLA纳米颗粒(SMNP)。含皂苷的佐剂表现出独特的作用机制,以肥大细胞依赖性方式改变淋巴流量,并促进抗原进入排水淋巴结。 SMNP特别有效,比小鼠中与成分相关的辅助AS01B表现出更大的效力,并且在非人类灵长类动物中启动了鲁棒的生发中心B细胞,TFH和HIV Tier 2中和抗体。这些发现共同阐明了有关皂苷佐剂可促进免疫反应的机制的新灯,并表明SMNP在HIV,SARS-COV-2和其他病原体的情况下可能是有前途的辅助者。

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