Australian Institute for Bioengineering and Nanotechnology, University of Queensland, St Lucia, QLD, 4072, Australia.
Vaccine Delivery, Animal Science, Agri-Science Queensland, Department of Agriculture & Fisheries, Dutton Park, QLD, 4102, Australia.
Small. 2018 May;14(19):e1704465. doi: 10.1002/smll.201704465. Epub 2018 Apr 14.
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.
纳米材料已被广泛测试作为新一代疫苗佐剂，但很少能引起有效的免疫反应。例如，粘土纳米粒子，层状双氢氧化物（LDH）和海泡石（HEC）纳米粒子，已显示出在产生有效和持久的免疫反应方面的强大佐剂活性。然而，粘土纳米佐剂刺激免疫系统的机制尚不清楚。在这里，证明 LDH 和 HEC-抗原复合物在培养基/血清中形成松散的聚集体。它们在皮下注射后在组织中也形成具有松散结构的结节，在那里它们作为储存库长达 35 天。更重要的是，粘土纳米颗粒主动且持续地将免疫细胞募集到储存库中长达一个月，并刺激比 FDA 批准的佐剂 Alum 和 QuilA 更强的免疫反应。在粘土纳米颗粒储存库中也观察到持续的抗原释放，在 35 天后释放 50-60%的抗原。相比之下，Alum-抗原复合物从储存库中释放出的抗原很少。重要的是，LDH 和 HEC 比 QuilA 和 Alum 更有效地促进记忆 T 细胞的增殖。这些发现表明，两种粘土纳米佐剂都可以作为持续和有效的免疫反应的主动疫苗平台。
