Stieneker F, Kersten G, van Bloois L, Crommelin D J, Hem S L, Löwer J, Kreuter J
Institut für Pharmazeutische Technologie, Johann Wolfgang Goethe-Universität, Frankfurt am Main-Niederusel, Germany.
Vaccine. 1995 Jan;13(1):45-53. doi: 10.1016/0264-410x(95)80010-b.
The objective of this study was the comparison of the quantity and quality of the humoral immune response against inactivated whole human immunodeficiency virus type 2. Twenty-four different adjuvants were tested. The toxicity of these preparations was determined. Due to the large number of experiments, the animal model used was the NMRI mouse. Sera were assayed for the presence of antibodies by ELISA and Western blot. The toxicity of the adjuvants was determined by observing lethal side-effects occurring within two days after injection of the immunogenic preparations. The results show that polymethylmethacrylate nanoprticles were the best overall adjuvant, inducing the highest titres of antibodies compared with other adjuvants as well as producing a significantly better immune response against a number of individual HIV-2 antigens without any observable toxic side-effects. However, this adjuvant did not induce antibodies against the outer envelope protein gp120, whereas such antibodies were induced by aluminium compounds, Freund's complete and incomplete adjuvants, and fumed silica (Aerosil). This result suggests the necessity of using vaccines with two or more different adjuvants in order to induce the required immune response against physically different antigens.
本研究的目的是比较针对灭活的全人免疫缺陷病毒2型的体液免疫反应的数量和质量。测试了24种不同的佐剂。测定了这些制剂的毒性。由于实验数量众多,所使用的动物模型是NMRI小鼠。通过ELISA和蛋白质印迹法检测血清中抗体的存在情况。通过观察注射免疫原性制剂后两天内出现的致命副作用来确定佐剂的毒性。结果表明,聚甲基丙烯酸甲酯纳米颗粒是总体上最好的佐剂,与其他佐剂相比,它诱导产生的抗体滴度最高,并且针对多种单个HIV-2抗原产生的免疫反应明显更好,且没有任何可观察到的毒性副作用。然而,这种佐剂不能诱导针对外膜蛋白gp120的抗体,而铝化合物、弗氏完全和不完全佐剂以及气相二氧化硅(Aerosil)能诱导产生此类抗体。这一结果表明,有必要使用含有两种或更多种不同佐剂的疫苗,以诱导针对物理性质不同的抗原产生所需的免疫反应。