卵清蛋白
免疫系统
抗原
粒径
生物物理学
粒子(生态学)
材料科学
纳米颗粒
抗原呈递
类病毒颗粒
化学
纳米技术
免疫学
生物
T细胞
生物化学
基因
物理化学
重组DNA
生态学
作者
Hemachand Tummala,Aaron C. Anselmo,Amrita Banerjee,Michael Zakrewsky,Samir Mitragotri
标识
DOI:10.1016/j.jconrel.2015.09.069
摘要
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.
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