Incorporation of CpG oligonucleotide ligand into protein-loaded particle vaccines promotes antigen-specific CD8 T-cell immunity
Incorporation of CpG oligonucleotide ligand into protein-loaded particle vaccines promotes antigen-specific CD8 T-cell immunity
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DOI：
10.1021/bc060165i
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发表时间：
2007-01-01
影响因子：
4.7
通讯作者：
Frechet, Jean M. J.
中科院分区：
文献类型：
--
作者：
Standley, Stephany M.;Mende, Ines;Frechet, Jean M. J.
多组分生物素载体的开发是药物递送领域中的重要挑战，特别是在基于蛋白质的疫苗领域。虽然将蛋白抗原递送至抗原呈递细胞（APC）对于这种类型的疫苗接种至关重要，但是为了产生更有效的免疫应答，掺入额外的佐剂可能同样重要。本文介绍了载体颗粒的合成和生物学评价，既提供了一个蛋白质的有效载荷的APC和显示受体配体的增强APC免疫刺激。合成展示Toll样受体9的CpG寡核苷酸配体的颗粒。向颗粒中添加CpG DNA导致白细胞介素-12（一种有助于T细胞活化的细胞因子）的分泌增加45倍，并且APC的共刺激分子的表达显著增加。此外，用含有卵清蛋白（OVA）和CpG DNA的颗粒接种诱导体内上级OVA特异性CD 8 T细胞应答，如通过增加的OVA特异性CD 8 T细胞增殖、促炎细胞因子IFN-γ的分泌和OVA特异性细胞毒性的诱导所测量的。
The development of multicomponent biotherapeutic carriers is an important challenge in the field of drug delivery, particularly in the area of protein-based vaccines. While the delivery of protein antigens to antigen presenting cells (APCs) is crucial for this type of vaccination, the incorporation of additional adjuvants may be just as important in order to generate more potent immune responses. This article presents the synthesis and biological evaluation of carrier particles that both deliver a protein payload to APCs and display receptor ligands for the enhancement of APC immunostimulation. Particles displaying CpG oligonucleotide ligands for Toll-like receptor 9 were synthesized. The addition of CpG DNA to the particles led to a 45-fold increase in the secretion of interleukin-12, a cytokine that aids in T-cell activation, and a significant increase in the expression of costimulatory molecules by APCs. Moreover, vaccination with particles containing both ovalbumin (OVA) and CpG DNA induced a superior OVA-specific CD8 T-cell response in vivo, as measured by increased OVA-specific CD8 T-cell proliferation, secretion of the proinflammatory cytokine IFN-gamma, and the induction of OVA-specific cytotoxicity.