Carman W F, Zanetti A R, Karayiannis P, Waters J, Manzillo G, Tanzi E, Zuckerman A J, Thomas H C
Department of Medicine, St Mary's Hospital Medical School, London, UK.
Lancet. 1990 Aug 11;336(8711):325-9. doi: 10.1016/0140-6736(90)91874-a.
In southern Italy, 44 contacts of hepatitis B virus carriers, including infants of carrier mothers, became HBsAg positive despite passive and active immunisation according to standard protocols. In 32 of these vaccinees infection was confirmed by the presence of additional markers of viral replication. In 1 infant, serious disease occurred. The virus from this patient is an escape mutant with a different sequence from that of the isolate from the mother. A point mutation from guanosine to adenosine at nucleotide position 587 resulted in an aminoacid substitution from glycine to arginine in the highly antigenic a determinant of HBsAg. This mutation is stable: it is present in an isolate from the child 5 years later. In some of these patients, including this child, the a determinant, to which a large part of the vaccine-induced immunity is directed, has been partly lost. Binding to HBsAg of a monoclonal antibody, previously mapped to the region of the mutation, was reduced in the child relative to that of the mother.
在意大利南部，44名乙肝病毒携带者的接触者，包括携带者母亲的婴儿，尽管按照标准方案进行了被动和主动免疫，仍出现乙肝表面抗原（HBsAg）阳性。在这些接种疫苗者中，有32人通过病毒复制的其他标志物证实感染。有1名婴儿发生了严重疾病。该患者的病毒是一种逃逸突变株，其序列与母亲的病毒分离株不同。核苷酸位置587处从鸟苷到腺苷的点突变导致乙肝表面抗原高抗原性a决定簇中的氨基酸从甘氨酸替换为精氨酸。这种突变是稳定的：5年后在该儿童的病毒分离株中仍存在。在包括该儿童在内的一些患者中，疫苗诱导的大部分免疫所针对的a决定簇已部分丧失。与母亲相比，该儿童中先前定位到突变区域的单克隆抗体与乙肝表面抗原的结合减少。
