Granoff D M, McHugh Y E, Raff H V, Mokatrin A S, Van Nest G A
Chiron Vaccines, Emeryville, California 94608, USA.
Infect Immun. 1997 May;65(5):1710-5. doi: 10.1128/iai.65.5.1710-1715.1997.
The ability of the adjuvant MF59 to enhance the immunogenicity of polysaccharide-protein conjugate vaccines was investigated in infant baboons. MF59 consists of stable droplets (<250 nm) of the metabolizable oil squalene and two surfactants, polyoxyethylene sorbitan monooleate and sorbitan trioleate, in an oil-in-water emulsion. In humans, MF59 is well tolerated and enhances the immunogenicity of recombinant protein subunit or particle vaccines. Its effect on the immunogenicity of polysaccharide-protein conjugate vaccines is unknown. Baboons 1 to 4 months of age were immunized intramuscularly with Neisseria meningitidis group C and Haemophilus influenzae type b (Hib) oligosaccharide-CRM197 conjugate vaccines. The lyophilized vaccines were reconstituted with phosphate-buffered saline (PBS), Al(OH)3 (alum), or MF59. Groups of five animals each were given three injections of the respective formulations, with one injection every 4 weeks. Four weeks after each immunization, the MF59 group had up to 7-fold-higher geometric mean anticapsular-antibody titers than the alum group and 5- to 10-fold-higher N. meningitidis group C bactericidal-antibody titers. Twenty-one weeks after the third immunization, the MF59 group still showed 5- to 10-fold-higher anticapsular-antibody titers. The antibody responses of the animals given the vaccines reconstituted with PBS were low at all times measured. Both the MF59 and alum groups, but not the PBS group, showed booster antibody responses to unconjugated Hib and N. meningitidis group C polysaccharides, results consistent with induction of memory B cells. Thus, MF59 may be useful for accelerating and augmenting immunity to polysaccharide-protein conjugate vaccines in infants.
在幼年狒狒中研究了佐剂 MF59 增强多糖 - 蛋白结合疫苗免疫原性的能力。MF59 由可代谢油角鲨烯的稳定液滴(<250 nm)以及两种表面活性剂聚氧乙烯山梨醇单油酸酯和山梨醇三油酸酯组成,呈水包油乳液。在人类中,MF59 耐受性良好,并能增强重组蛋白亚基或颗粒疫苗的免疫原性。其对多糖 - 蛋白结合疫苗免疫原性的影响尚不清楚。对 1 至 4 月龄的狒狒进行了脑膜炎奈瑟菌 C 群和 b 型流感嗜血杆菌(Hib)寡糖 - CRM197 结合疫苗的肌肉注射免疫接种。冻干疫苗用磷酸盐缓冲盐水(PBS)、氢氧化铝(明矾)或 MF59 复溶。每组五只动物分别接受三次相应制剂的注射,每 4 周注射一次。每次免疫接种后 4 周,MF59 组的几何平均抗荚膜抗体滴度比明矾组高 7 倍,脑膜炎奈瑟菌 C 群杀菌抗体滴度高 5 至 10 倍。第三次免疫接种后 21 周,MF59 组的抗荚膜抗体滴度仍高 5 至 10 倍。在所有测量时间点,用 PBS 复溶疫苗的动物抗体反应均较低。MF59 组和明矾组,但不是 PBS 组,对未结合的 Hib 和脑膜炎奈瑟菌 C 群多糖均表现出加强抗体反应,结果与记忆 B 细胞的诱导一致。因此,MF59 可能有助于加速和增强婴儿对多糖 - 蛋白结合疫苗的免疫。