Hollow microneedle-mediated intradermal delivery of model vaccine antigen-loaded PLGA nanoparticles elicits protective T cell-mediated immunity to an intracellular bacterium
Hollow microneedle-mediated intradermal delivery of model vaccine antigen-loaded PLGA nanoparticles elicits protective T cell-mediated immunity to an intracellular bacterium
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DOI：
10.1016/j.jconrel.2017.09.017
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发表时间：
2017-11-28
影响因子：
10.8
通讯作者：
Sijts, Alice J. A. M.
中科院分区：
文献类型：
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作者：
de Groot, Anne Marit;Du, Guangsheng;Sijts, Alice J. A. M.
由于存在大量表皮和真皮抗原呈递细胞，皮肤是用于免疫的有吸引力的器官。空心微针允许疫苗的精确和非侵入性皮内递送。在这项研究中，卵清蛋白（OVA）负载聚（乳酸-共-乙醇酸）（PLGA）纳米粒子与和没有TLR 3激动剂聚（I：C）的制备和管理的皮内空心微针。检查了PLGA纳米颗粒诱导细胞毒性T细胞应答的能力，有助于保护免受细胞内病原体的侵害。我们发现，与可溶性OVA相比，单次注射OVA负载的PLGA纳米颗粒以显著高的效率引发了过继转移的抗原特异性幼稚转基因CD 8（+）和CD 4（+）T细胞。应用三重免疫方案，PLGA纳米颗粒也引发内源性OVA特异性CD 8（+）T细胞。在用特别是与OVA和聚（LC）共包封的阴离子PLGA纳米颗粒免疫后的免疫应答提供了针对分泌OVA的细胞内细菌单核细胞增生李斯特菌的重组菌株的保护。两者合计，我们表明，PLGA纳米颗粒制剂是一个很好的蛋白质抗原进入皮肤和保护性细胞免疫反应，可以诱导使用空心微针皮内免疫。
The skin is an attractive organ for immunization due to the presence of a large number of epidermal and dermal antigen-presenting cells. Hollow microneedles allow for precise and non-invasive intradermal delivery of vaccines. In this study, ovalbumin (OVA)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles with and without TLR3 agonist poly(I:C) were prepared and administered intradermally by hollow microneedles. The capacity of the PLGA nanoparticles to induce a cytotoxic T cell response, contributing to protection against intracellular pathogens, was examined. We show that a single injection of OVA-loaded PLGA nanoparticles, compared to soluble OVA, primed both adoptively transferred antigen-specific naive transgenic CD8(+) and CD4(+) T cells with markedly high efficiency. Applying a triple immunization protocol, PLGA nanoparticles primed also endogenous OVA-specific CD8(+) T cells. Immune response, following immunization with in particular anionic PLGA nanoparticles co-encapsulated with OVA and poly(LC), provided protection against a recombinant strain of the intracellular bacterium Listeria monocytogenes, secreting OVA. Taken together, we show that PLGA nanoparticle formulation is an excellent delivery system for protein antigen into the skin and that protective cellular immune responses can be induced using hollow microneedles for intradermal immunizations.