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Clay Nanoparticles Elicit Long‐Term Immune Responses by Forming Biodegradable Depots for Sustained Antigen Stimulation
Small ( IF 13.3 ) Pub Date : 2018-04-14 , DOI: 10.1002/smll.201704465
Weiyu Chen 1 , Huali Zuo 1 , Bei Li 1 , Chengcheng Duan 1 , Barbara Rolfe 1 , Bing Zhang 2 , Timothy J. Mahony 3 , Zhi Ping Xu 1
Affiliation  

Nanomaterials have been widely tested as new generation vaccine adjuvants, but few evoke efficient immunoreactions. Clay nanoparticles, for example, layered double hydroxide (LDH) and hectorite (HEC) nanoparticles, have shown their potent adjuvanticity in generating effective and durable immune responses. However, the mechanism by which clay nanoadjuvants stimulate the immune system is not well understood. Here, it is demonstrated that LDH and HEC–antigen complexes form loose agglomerates in culture medium/serum. They also form nodules with loose structures in tissue after subcutaneous injection, where they act as a depot for up to 35 d. More importantly, clay nanoparticles actively and continuously recruit immune cells into the depot for up to one month, and stimulate stronger immune responses than FDA‐approved adjuvants, Alum and QuilA. Sustained antigen release is also observed in clay nanoparticle depots, with 50–60% antigen released after 35 d. In contrast, Alum–antigen complexes show minimal antigen release from the depot. Importantly, LDH and HEC are more effective than QuilA and Alum in promoting memory T‐cell proliferation. These findings suggest that both clay nanoadjuvants can serve as active vaccine platforms for sustained and potent immune responses.

中文翻译:

黏土纳米颗粒通过形成可生物降解的长效抗原刺激抗原来激发长期的免疫反应。

纳米材料已被广泛测试为新一代疫苗佐剂,但很少能引起有效的免疫反应。粘土纳米颗粒,例如层状双氢氧化物(LDH)和锂蒙脱石(HEC)纳米颗粒,在产生有效和持久的免疫反应中表现出强大的辅助作用。但是,粘土纳米佐剂刺激免疫系统的机制尚不十分清楚。在这里,证明了LDH和HEC-抗原复合物在培养基/血清中形成松散的团块。皮下注射后,它们还会在组织中形成结节,结节具有松散的结构,在这里它们可充当长达35天的贮库。更重要的是,粘土纳米颗粒可主动连续地将免疫细胞募集到仓库中长达一个月,并且比FDA批准的佐剂Alum和QuilA刺激更强的免疫反应。在黏土纳米颗粒储库中也观察到了持续的抗原释放,在35天后释放了50-60%的抗原。相比之下,明矾-抗原复合物显示出从储库中释放的抗原最少。重要的是,LDH和HEC在促进记忆T细胞增殖方面比QuilA和Alum更有效。这些发现表明,两种粘土纳米佐剂均可以用作持续和有效免疫应答的活性疫苗平台。
更新日期:2018-04-14
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