Gregoriadis G, Tan L, Ben-Ahmeida E T, Jennings R
Centre for Drug Delivery Research, School of Pharmacy, University of London, UK.
Vaccine. 1992;10(11):747-53. doi: 10.1016/0264-410x(92)90509-i.
Reconstituted influenza virus (A/PR/8 strain) envelopes (RIVE) and influenza virus (A/Sichuan/87 (H3N2) strain) surface antigens were entrapped in dehydration-rehydration vesicles (DRV liposomes) composed of egg phosphatidylcholine (PC) or distearoyl phosphatidylcholine (DSPC DRV) and equimolar (32 mumol) cholesterol. Entrapment values for RIVE were 31.2 (PC) and 29.4% (DSPC DRV) of the material used. Corresponding entrapment values for the A/Sichuan/87 strain antigens were 40.7 and 39.3%. Balb/c mice injected intramuscularly with PC or DSPC DRV liposomes containing 0.1 and 1.0 microgram RIVE exhibited primary (higher dose only) and secondary responses (IgG1) which were significantly higher than those obtained in mice injected with identical amounts of non-entrapped RIVE. Significantly higher secondary responses were also observed for the IgG2a and IgG2b subclasses. In experiments designed to assess the effectiveness of DRV liposomes as a carrier of influenza virus antigens in a potential vaccine, hamsters were immunized intramuscularly with 0.1, 0.5 and 5.0 micrograms of free or liposome-entrapped influenza A/Sichuan/87 surface antigens. Results showed increased haemagglutination inhibition (HI) antibody levels in terms of both primary (0.5 and 5.0 micrograms doses) and secondary (all doses) responses in the sera of animals treated with the liposomal formulations. DSPC compared with PC DRV exhibited greater adjuvanticity when the lower doses of antigens were used.
重组流感病毒(A/PR/8株)包膜(RIVE)和流感病毒(A/四川/87(H3N2)株)表面抗原被包裹于由鸡蛋磷脂酰胆碱(PC)或二硬脂酰磷脂酰胆碱(DSPC DRV)与等摩尔(32微摩尔)胆固醇组成的脱水-再水化囊泡(DRV脂质体)中。RIVE的包裹率分别为所用材料的31.2%(PC)和29.4%(DSPC DRV)。A/四川/87株抗原的相应包裹率分别为40.7%和39.3%。给Balb/c小鼠肌肉注射含有0.1微克和1.0微克RIVE的PC或DSPC DRV脂质体,其初次反应(仅高剂量组)和二次反应(IgG1)显著高于注射等量未包裹RIVE的小鼠。IgG2a和IgG2b亚类的二次反应也显著更高。在旨在评估DRV脂质体作为流感病毒抗原潜在疫苗载体有效性的实验中,给仓鼠肌肉注射0.1微克、0.5微克和5.0微克游离或脂质体包裹的甲型流感病毒A/四川/87表面抗原。结果显示,在脂质体制剂处理的动物血清中,初次反应(0.5微克和5.0微克剂量组)和二次反应(所有剂量组)的血凝抑制(HI)抗体水平均有所升高。当使用较低剂量抗原时,与PC DRV相比,DSPC DRV表现出更强的佐剂活性。