Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97331, United States.
J Control Release. 2010 Jan 4;141(1):93-100. doi: 10.1016/j.jconrel.2009.08.023. Epub 2009 Sep 1.
An accumulation of research over the years has demonstrated the utility of nanoparticles as antigen carriers with adjuvant activity. Herein we defined the adjuvanticity of a novel lecithin-based nanoparticle engineered from emulsions. The nanoparticles were spheres of around 200nm. Model protein antigens, bovine serum albumin (BSA) or Bacillus anthracis protective antigen (PA) protein, were covalently conjugated onto the nanoparticles. Mice immunized with the BSA-conjugated nanoparticles developed strong anti-BSA antibody responses comparable to that induced by BSA adjuvanted with incomplete Freund's adjuvant and 6.5-fold stronger than that induced by BSA adsorbed onto aluminum hydroxide. Immunization of mice with the PA-conjugated nanoparticles elicited a quick, strong, and durable anti-PA antibody response that afforded protection of the mice against a lethal dose of anthrax lethal toxin challenge. The potent adjuvanticity of the nanoparticles was likely due to their ability to move the antigens into local draining lymph nodes, to enhance the uptake of the antigens by antigen-presenting cells (APCs), and to activate APCs. This novel nanoparticle system has the potential to serve as a universal protein-based vaccine carrier capable of inducing strong immune responses.
多年来的研究积累证明了纳米颗粒作为具有佐剂活性的抗原载体的效用。在此,我们定义了一种新型基于卵磷脂的纳米颗粒的佐剂特性,该纳米颗粒由乳液工程化而成。这些纳米颗粒呈约 200nm 的球体。模型蛋白抗原,牛血清白蛋白(BSA)或炭疽保护性抗原(PA)蛋白,通过共价键连接到纳米颗粒上。用 BSA 缀合的纳米颗粒免疫的小鼠产生了与用不完全弗氏佐剂佐剂的 BSA 诱导的相当的强抗 BSA 抗体反应,比吸附在氢氧化铝上的 BSA 诱导的强 6.5 倍。用 PA 缀合的纳米颗粒免疫的小鼠引发了快速、强烈和持久的抗 PA 抗体反应,使小鼠能够抵御炭疽致死毒素的致死剂量的攻击。纳米颗粒的强效佐剂作用可能归因于其将抗原转移到局部引流淋巴结的能力,增强抗原呈递细胞(APC)对抗原的摄取能力,并激活 APC。这种新型纳米颗粒系统有可能成为一种通用的基于蛋白质的疫苗载体,能够诱导强烈的免疫反应。