McAleer W J, Markus H Z, Wampler D E, Buynak E B, Miller W J, Weibel R E, McLean A A, Hilleman M R
Proc Soc Exp Biol Med. 1984 Mar;175(3):314-9. doi: 10.3181/00379727-175-41801.
Vaccine against human hepatitis B was prepared using antigen derived from hepatitis B carrier hepatoma cells grown in the interstices of a Diaflo hollow filter unit. Hepatitis B surface antigen (HBsAg) produced by these cells was purified by immune affinity chromatography, digestion with DNase and pepsin, and Sephadex G-150 separation. The Formalin-treated antigen was formulated in 20-micrograms dose on alum adjuvant with thimerosal added as a preservative. This cell culture vaccine was as potent as human plasma-derived vaccine as measured in a mouse potency assay. The vaccine proved safe in tests in chimpanzees and in human subjects who were in late stages of cancer of the central nervous system and who were receiving therapy for their condition. None of five subjects who received the vaccine developed untoward clinical reactions. Two of the subjects who received all three doses of vaccine developed antibody against HBsAg. Three persons, two given only the primary doses and one who was given all three doses but was lost to follow-up, demonstrated no response. The slow and relatively low antibody responses to the vaccine were similar to those in other immunosuppressed persons who were given vaccine of human plasma origin.
利用在Diaflo中空过滤单元间隙中生长的乙肝携带者肝癌细胞衍生的抗原制备了人用乙肝疫苗。这些细胞产生的乙肝表面抗原(HBsAg)通过免疫亲和层析、用DNA酶和胃蛋白酶消化以及Sephadex G - 150分离进行纯化。经福尔马林处理的抗原以20微克剂量与明矾佐剂配制成型,并添加硫柳汞作为防腐剂。在小鼠效力试验中,这种细胞培养疫苗与源自人血浆的疫苗效力相当。在黑猩猩以及处于中枢神经系统癌症晚期且正在接受治疗的人类受试者的试验中,该疫苗被证明是安全的。接受疫苗的五名受试者均未出现不良临床反应。接受全部三剂疫苗的两名受试者产生了抗HBsAg抗体。三名受试者,两名仅接种了初始剂量,一名接种了全部三剂但失访,均未出现反应。对该疫苗的缓慢且相对较低的抗体反应与其他接受源自人血浆疫苗的免疫抑制者的反应相似。