Nanoparticles and antigen delivery: understanding the benefits and drawbacks of different delivery platforms.
Nanoparticles and antigen delivery: understanding the benefits and drawbacks of different delivery platforms.
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DOI：
10.2217/nnm.14.16
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发表时间：
2014-05
期刊：
影响因子：
5.5
通讯作者：
N. Fischer;A. Rasley;C. Blanchette
中科院分区：
文献类型：
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作者：
N. Fischer;A. Rasley;C. Blanchette
疫苗接种在历史上已被证明是控制和在某些情况下根除传染病的最有效的预防方法之一[1]。虽然目前常规使用的大多数疫苗是由减毒活疫苗或灭活的全细菌或病毒组成的全生物体疫苗[2]，但基于分离的蛋白质、肽或多糖的亚单位疫苗是目前开发新疫苗或改进疫苗的研究工作的主要焦点。由于许多原因，亚单位疫苗制剂是有吸引力的前景。首先，通过消除使用减毒或完全灭活的病原体的需要，通过消除使用减毒或完全灭活的病原体的需要，亚单位抗原的安全性增加，亚单位抗原提供了增强的安全性特征，更简化的制造过程，并扩大了其在免疫抑制个体中使用的适用性[3]。其次，亚单位疫苗制剂的反应原性明显低于其他疫苗[3]。第三，亚单位疫苗明显更纯，易于表征，改善了疫苗制剂的质量控制[3-5]。然而，亚单位抗原的整体简单性和纯度是有代价的。当单独使用时，特别是在重组蛋白的情况下，这些制剂通常缺乏引发适当宿主免疫应答所需的必要免疫刺激特性[5]。因此，亚单位抗原需要与免疫刺激化合物或佐剂共同施用，例如单磷酰脂质A（MPLA）、未甲基化的CpG寡核苷酸（CpGs）、α-半乳糖神经酰胺（GalCer）、鞭毛蛋白、胞壁酰二肽、基于皂苷的佐剂（例如，QS-21）和免疫刺激复合物，以引发适当的保护性免疫应答[6]。尽管这些佐剂已显示在简单地与亚单位抗原共配制和施用时诱导免疫应答，但通常需要高佐剂剂量来引发足够强的应答以提高抗原效力。高佐剂剂量的必要性可能是由于多种因素的组合，包括佐剂溶解度和摄取效率，这可能影响树突状细胞活化和刺激的空间和时间协调。纳米颗粒提供了减轻这些因素中的一些的手段，主要是通过提供可溶性平台，该可溶性平台可以最佳地适应潜在不同的化学物质，并且由于纳米颗粒的固有生物分布特征和摄取动力学[7]或通过物理共定位[8，9]而确保抗原和佐剂的同步摄取。
Vaccination has been shown historically to be one of the most effective prevention methods for controlling, and in some cases eradicating, infectious disease [1]. While the majority of vaccines used routinely today are wholeorganism vaccines consisting of either live attenuated vaccines or killed whole bacteria or viruses [2], subunit vaccines based on isolated proteins, peptides or polysaccharaides are the main focus of current research efforts in the development of new or improved vaccines. Subunit vaccine formulations are an attractive prospect for a number of reasons. First, by eliminating the need to utilize attenuated or whole killed pathogens the increased safety of subunit antigens, afforded by eliminating the need to utilize attenuated or whole killed pathogens, subunit antigens offer enhanced safety profiles, more simplified manufacture processes and broadens their applicability for use in immunosuppressed individuals [3]. Second, subunit vaccine formulations are significantly less reactogenic than other vaccines [3]. Third, subunit vaccines are significantly more pure and can be readily characterized, improving quality control of the vaccine preparations [3–5]. The overall simplicity and purity of the subunit antigens, however, comes at a price. When used alone, especially in the case of recombinant proteins, these formulations often lack the necessary immunostimulatory properties required to elicit the appropriate host immune response [5]. Therefore, subunit antigens require coadministration with immune-stimulating compounds or adjuvants, such as monophosphoryl lipid A (MPLA), unmethylated CpG oligonucleotides (CpGs), α-galactosylceramide (GalCer), flagellin, muramyl dipeptide, saponin-based adjuvants (e.g., QS-21) and immune-stimulating complexes, to elicit appropriate protective immune responses [6]. Although these adjuvants have been shown to induce immune responses when simply coformulated and administered with a subunit antigen, high adjuvant doses are often required to elicit a strong enough response to improve antigen efficacy. The necessity of high adjuvant doses is likely due to a combination of factors, including adjuvant solubility and uptake efficiency, which may impact spatial and temporal coordination of dendritic cell activation and stimulation. Nanoparticles provide a means of mitigating some of these factors, primarily by providing a soluble platform that can optimally accommodate potentially disparate chemistries and ensure synchronized uptake of both antigen and adjuvant due to the nanoparticle’s inherent biodistribution profile and uptake dynamics [7] or through physical co-localization [8,9].