Center for Bioengineering, Department of Chemical Engineering, University of California, Santa Barbara, CA 93106, United States.
Center for Bioengineering, Department of Chemical Engineering, University of California, Santa Barbara, CA 93106, United States.
J Control Release. 2015 Dec 28;220(Pt A):141-148. doi: 10.1016/j.jconrel.2015.09.069. Epub 2015 Oct 3.
The immune system has evolved to recognize and respond to a wide variety of pathogens and produce distinct immune responses against diverse pathogenic structures. Despite remarkable advances, the general mechanisms by which the immune system differentiates the structure of antigen presenting particulates have yet to be elucidated. Using particles of various sizes and shapes, we assessed the role of morphological features of particles in antigen presentation and subsequent processing by the immune cells. Ovalbumin was used as a model antigen. Spherical polystyrene particles of 193 nm and 521 nm diameters were successfully stretched to form rod-shaped particles of 376 nm and 1530 nm in length, respectively. Ovalbumin conjugation to these different particle types was optimized to achieve ~50 μg of ovalbumin conjugation per mg of particle. In vivo immunization study results revealed that small spherical particles (193 nm in diameter) produced a Th1-biased response whereas rod-shaped particles (1530 nm in length) produced a Th2-biased response against ovalbumin. Among different particle types, smaller spherical (193 nm) particles generated stronger Th1 and Th2 immune responses compared to the other particle types. In vitro studies with dendritic cells indicated that spherical (193 nm) and rod (1530 nm) shaped particles were internalized by dendritic cells and delivered ovalbumin. These results provide evidence for size- and shape-dependent modulation of immune responses and this knowledge can be leveraged to rationally design and develop next generation vaccines against a wide range of pathogens.
免疫系统已经进化到能够识别和应对各种各样的病原体，并针对不同的病原体结构产生独特的免疫反应。尽管取得了显著的进展，但免疫系统区分抗原呈递颗粒结构的一般机制尚未阐明。我们使用各种大小和形状的颗粒来评估颗粒的形态特征在抗原呈递和随后的免疫细胞处理中的作用。卵清蛋白被用作模型抗原。将 193nm 和 521nm 直径的球形聚苯乙烯颗粒成功拉伸，分别形成 376nm 和 1530nm 长的棒状颗粒。优化了这些不同颗粒类型的卵清蛋白缀合，以实现每毫克颗粒约 50μg 的卵清蛋白缀合。体内免疫研究结果表明，小的球形颗粒（直径 193nm）产生 Th1 偏向的反应，而棒状颗粒（长 1530nm）产生 Th2 偏向的反应对抗原卵清蛋白。在不同的颗粒类型中，与其他颗粒类型相比，较小的球形（193nm）颗粒产生更强的 Th1 和 Th2 免疫反应。与树突状细胞的体外研究表明，球形（193nm）和棒状（1530nm）颗粒被树突状细胞内化，并递呈卵清蛋白。这些结果为大小和形状依赖的免疫反应调节提供了证据，并且可以利用这些知识来合理设计和开发针对广泛病原体的下一代疫苗。
