Department of Biomedical Engineering, The University of Texas, Austin, TX 78712, USA.
Adv Healthc Mater. 2013 Jan;2(1):72-94. doi: 10.1002/adhm.201200268. Epub 2012 Dec 6.
The development and widespread application of vaccines has been one of the most significant achievements of modern medicine. Vaccines have not only been instrumental in controlling and even eliminating life-threatening diseases like polio, measles, diphtheria, etc., but have also been immensely powerful in enhancing the worldwide outlook of public health over the past century. Despite these successes, there are still many complex disorders (e.g., cancer, HIV, and other emerging infectious diseases) for which effective preventative or therapeutic vaccines have been difficult to develop. This failure can be attributed primarily to our inability to precisely control and modulate the highly complex immune memory response, specifically the cellular response. Dominated by B and T cell maturation and function, the cellular response is primarily initiated by potent immunostimulators and antigens. Efficient and targeted delivery of these immunomodulatory and immunostimulatory molecules to appropriate cells is key to successful development of next generation vaccine formulations. Over the past decade, particulate carriers have emerged as an attractive means for enhancing the delivery efficacy and potency of vaccines and associated immunomodulatory molecules. Specifically, polymer-based micro and nanoparticles are being extensively studied for a wide variety of applications. In this review, we discuss the immunological fundamentals for developing effective vaccines and how materials and material properties can be exploited to improve these therapies. Particular emphasis is given to polymer-based particles and how the route of administration of particulate systems affects the phenotype and robustness of an immune response. Comparison of various strategies and recent advancements in the field are discussed along with insights into current limitations and future directions.
疫苗的开发和广泛应用是现代医学最显著的成就之一。疫苗不仅在控制甚至消除脊髓灰质炎、麻疹、白喉等危及生命的疾病方面发挥了重要作用,而且在过去一个世纪中极大地增强了全球公共卫生的前景。尽管取得了这些成功,但仍有许多复杂的疾病(例如癌症、HIV 和其他新发传染病)难以开发出有效的预防或治疗性疫苗。这种失败主要归因于我们无法精确控制和调节高度复杂的免疫记忆反应,特别是细胞反应。细胞反应主要由 B 和 T 细胞成熟和功能主导,由有效的免疫刺激剂和抗原引发。将这些免疫调节和免疫刺激分子高效且靶向递送至适当的细胞是成功开发下一代疫苗制剂的关键。在过去的十年中,颗粒载体已成为增强疫苗和相关免疫调节分子递送效果和效力的一种有吸引力的手段。具体而言,基于聚合物的微球和纳米球正被广泛研究用于各种应用。在本综述中,我们讨论了开发有效疫苗的免疫学基础,以及如何利用材料和材料特性来改善这些疗法。特别强调了基于聚合物的颗粒,以及颗粒系统的给药途径如何影响免疫反应的表型和稳健性。讨论了各种策略的比较以及该领域的最新进展,并深入探讨了当前的局限性和未来的方向。