Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana 47907-2091.
Novartis Vaccines and Diagnostics, Cambridge, Massachusetts 02139; MedImmune, Mountain View, California 94043.
J Pharm Sci. 2011 Aug;100(8):3245-3250. doi: 10.1002/jps.22555. Epub 2011 Mar 18.
The importance of the strength of antigen adsorption by aluminum-containing adjuvants on immunopotentiation was studied using HIV 1 SF162dV2gp140 (gp140), a potential HIV/AIDS antigen. The strengths of adsorption by aluminum hydroxide (AH) adjuvant and aluminum phosphate adjuvant, as measured by the Langmuir adsorptive coefficient, were 1900 and 400 mL/mg, respectively. The strength of adsorption by AH was modified by pretreatment of AH with two different concentrations of potassium dihydrogen phosphate to produce phosphate-treated aluminum hydroxide adjuvants having adsorptive coefficients of 1200 and 800 mL/mg. The four adjuvants were used to prepare vaccines containing either 1 or 10 μg of gp140 per dose. Antibody studies in mice revealed that the presence of an adjuvant increased the immune response in comparison with a solution of gp140 when the dose was 1 μg. Furthermore, the immune response was inversely related to the adsorptive coefficient. In contrast, no significant difference in immunopotentiation was observed between treatments in the presence or absence of an adjuvant when the dose of gp140 was 10 μg. Analysis of the binding of gp140 to CD4 and anti-gp140 monoclonal antibodies by surface plasmon resonance suggests that tight binding induced structural changes in the antigen.
研究了含铝佐剂对铝吸附抗原的强度在免疫增强中的重要性，所用的抗原是 HIV-1 SF162dV2gp140（gp140），这是一种有希望的 HIV/AIDS 抗原。用 Langmuir 吸附系数测量，氢氧化铝（AH）佐剂和磷酸铝佐剂的吸附强度分别为 1900 和 400 mL/mg。用两种不同浓度的磷酸二氢钾预处理 AH 来修饰 AH 的吸附强度，得到吸附系数分别为 1200 和 800 mL/mg 的磷酸处理的氢氧化铝佐剂。用这四种佐剂制备了每剂含有 1 或 10 μg gp140 的疫苗。在小鼠中的抗体研究表明，与 gp140 溶液相比，当剂量为 1 μg 时，佐剂的存在增加了免疫反应。此外，免疫反应与吸附系数成反比。相比之下，当 gp140 的剂量为 10 μg 时，佐剂的存在与否对免疫增强没有明显影响。表面等离子体共振分析 gp140 与 CD4 和抗 gp140 单克隆抗体的结合表明，紧密结合诱导了抗原的结构变化。
