O'Hagan D T, Ugozzoli M, Barackman J, Singh M, Kazzaz J, Higgins K, Vancott T C, Ott G
Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA.
Vaccine. 2000 Mar 6;18(17):1793-801. doi: 10.1016/s0264-410x(99)00522-8.
Novel adjuvant formulations involving PLG microparticles with entrapped recombinant protein antigens (env gp120 and p24 gag) from human immunodeficiency virus type-1 (HIV-1), dispersed in the emulsion adjuvant MF59 were evaluated as potential HIV-1 vaccine candidates in mice and baboons. In mice, the adjuvant combination induced significantly enhanced antibody responses in comparison to either adjuvant used alone. In addition, the polylactide co-glycolide polymer (PLG) microparticles and MF59 combination induced CTL activity against HIV-1 p24 gag. In baboons, the adjuvant combination induced significantly enhanced antibody titers after a single dose of gp120, but the responses were comparable to gp120 in MF59 alone after boosting. Both MF59+gp120 alone and PLG/gp120 in MF59 induced neutralizing antibodies against a T cell line-adapted (TCLA) strain and a primary isolate of HIV-1. In contrast to the observations with gp120, immunization in baboons with PLG/p24 in MF59 induced significantly enhanced antibody responses after boosting, in comparison to immunization with MF59 alone + p24.
对新型佐剂配方进行了评估,该配方包含包裹有来自1型人类免疫缺陷病毒(HIV-1)的重组蛋白抗原(env gp120和p24 gag)的聚乳酸-羟基乙酸共聚物(PLG)微粒,分散于乳液佐剂MF59中,以此作为小鼠和狒狒潜在的HIV-1疫苗候选物。在小鼠中,与单独使用任何一种佐剂相比,这种佐剂组合诱导的抗体反应显著增强。此外,聚乳酸-羟基乙酸共聚物(PLG)微粒与MF59的组合诱导了针对HIV-1 p24 gag的细胞毒性T淋巴细胞(CTL)活性。在狒狒中,单剂量接种gp120后,这种佐剂组合诱导的抗体滴度显著增强,但加强免疫后,其反应与单独使用MF59中的gp120相当。单独的MF59+gp120以及MF59中的PLG/gp120均诱导产生了针对T细胞系适应株(TCLA)和一种HIV-1原始分离株的中和抗体。与gp120的观察结果相反,与单独使用MF59+p24免疫相比,在狒狒中用MF59中的PLG/p24免疫在加强免疫后诱导的抗体反应显著增强。