Thomssen R, Gerlich W H, Böttcher U, Legler K, Ritter S, Stibbe W, Weinmann W, Klinge O, Pfeifer U
Dev Biol Stand. 1983;54:23-31.
No experimental setting is available to exclude residual infectivity in HBsAg vaccines derived from human plasma. Thus, safety can be achieved only by means of their preparation. To reduce infectivity of the starting material, only plasma from healthy anti-HBe positive donors was used. In the FRG, 50% of all healthy HBsAg carriers with anti-HBe have a suitable serum level of 5 to 20 micrograms/ml. The purification procedure removed hepatitis B virus by a factor greater than 10(4). The purified product contained only the HBsAg proteins and no serum protein, as shown by SDS gel electrophoresis. The pure HBsAg was treated with formalin 1:500 at 37 degrees C for 4 days. A loss of 30 to 50% antigenicity was tolerated to achieve the highest possible destruction of known and unknown infectious agents. After inactivation, the HBsAg was bound to aluminium hydroxide gel. The gel was washed repeatedly to remove the formalin. Doses of 40 micrograms or 20 micrograms absorbed HBsAg protein were given to greater than 2500 persons without serious side effects. In greater than 97% anti-HBs was formed with a median titer of 1900 I.U./ml.
目前没有实验装置可排除源自人血浆的乙肝表面抗原（HBsAg）疫苗中的残余传染性。因此，只能通过其制备方法来确保安全性。为降低起始原料的传染性，仅使用来自健康的抗HBe阳性供体的血浆。在联邦德国，所有健康的抗HBe阳性HBsAg携带者中，50%的人血清水平在5至20微克/毫升之间，较为合适。纯化程序可使乙肝病毒减少超过10⁴倍。如SDS凝胶电泳所示，纯化产物仅含HBsAg蛋白，不含血清蛋白。将纯HBsAg在37℃下用1:500的福尔马林处理4天。为尽可能彻底地杀灭已知和未知传染源，允许抗原性损失30%至50%。灭活后，将HBsAg与氢氧化铝凝胶结合。反复冲洗凝胶以去除福尔马林。给2500多人注射了40微克或20微克吸附了HBsAg蛋白的剂量，未出现严重副作用。超过97%的人产生了抗HBs，中位滴度为1900国际单位/毫升。
