Cheng Yu-Jhen, Huang Chiung-Yi, Ho Hui-Min, Huang Ming-Hsi
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, 35053 Miaoli, Taiwan.
Graduate Institute of Biomedical Sciences, China Medical University, 40402 Taichung, Taiwan.
Colloids Surf A Physicochem Eng Asp. 2021 Jan 5;608:125564. doi: 10.1016/j.colsurfa.2020.125564. Epub 2020 Sep 10.
Aluminum-containing salts are commonly used as antacids and vaccine adjuvants; however, key features of functional activities remain unclear. Here, we characterized vaccine formulations based on aluminum phosphate and aluminum hydroxide and investigated the respective modes of action linking physicochemical properties and catalytic ability. TEM microscopy indicated that aluminum phosphate gel solutions are amorphous, whereas aluminum hydroxide gel solutions have a crystalline structure consistent with boehmite. At very low BSA concentrations, 100 % adsorption of the protein on aluminum hydroxide could be achieved. As the protein concentration increased, the amount of adsorbed BSA decreased as fewer vacant sites were available on the surface of the adjuvants. Notably, less than 20 % adsorption was observed in aluminum phosphate. The protein adsorption profiles should confront the requirements for vaccine immunoavailability. In terms of catalytic ability, the prepared aluminum salts were tested for their ability to drive the amphiphilic engineering of oligo(lactic acid) (OLA) onto methoxy poly(ethylene glycol). It was concluded that aluminum hydroxide, rather than aluminum phosphate, is suitable to be a vaccine adjuvant according to the morphology and antigen adsorption efficiency results; on the other hand, aluminum phosphate may be a more efficient catalyst for the synthesis of polymeric emulsifiers than aluminum hydroxide. The results provide critical mechanistic insight into aluminum-containing salts in vaccine formulations.
含铝盐通常用作抗酸剂和疫苗佐剂;然而,其功能活性的关键特征仍不清楚。在此,我们对基于磷酸铝和氢氧化铝的疫苗制剂进行了表征,并研究了将物理化学性质与催化能力联系起来的各自作用模式。透射电子显微镜(TEM)显示,磷酸铝凝胶溶液是无定形的,而氢氧化铝凝胶溶液具有与勃姆石一致的晶体结构。在非常低的牛血清白蛋白(BSA)浓度下,蛋白质在氢氧化铝上的吸附率可达100%。随着蛋白质浓度的增加,吸附的BSA量减少,因为佐剂表面可用的空位较少。值得注意的是,在磷酸铝中观察到的吸附率不到20%。蛋白质吸附情况应符合疫苗免疫可用性的要求。在催化能力方面,测试了所制备的铝盐驱动聚(乳酸)(OLA)在甲氧基聚(乙二醇)上进行两亲性工程的能力。根据形态学和抗原吸附效率结果得出结论,氢氧化铝而非磷酸铝适合作为疫苗佐剂;另一方面,磷酸铝可能比氢氧化铝更有效地催化合成聚合物乳化剂。这些结果为疫苗制剂中含铝盐提供了关键的作用机制见解。