He J W, Lu Q, Zhu Q R, Duan S C, Wen Y M
Department of Molecular Virology, Shanghai Medical University, People's Republic of China.
Vaccine. 1998 Jan-Feb;16(2-3):170-3. doi: 10.1016/s0264-410x(97)00182-5.
Twenty-four infants who became positive to the surface antigen of hepatitis B virus (HBsAg) despite a complete course of active postexposure immunization with plasma derived hepatitis B vaccine were studied. The polymerase chain reaction amplified products of the common neutralizing epitope 'a' determinant of HBsAg (Nucleotide 419-598) from serum samples were sequenced and analyzed for nucleotide mutations. Four cases (16.7%) had mutations that led to amino acid substitutions between codons 124 and 147. Only one case (N1) showed a substitution at codon 145 (from glycine to arginine, 145R), the other three were at codons 126-129. The mother of N1 was co-infected with the wild type and the mutant virus. Five years later, serum of N1 showed only the wild type virus. There was no significant relationship between the mutation rate and the anti-HBs response to hepatitis B vaccination. Results suggest that without immune selective pressure, 145R variant was not frequently observed, and was not stable. Mutation in the 'a' determinant was not an important cause of failure to prevent maternal-infant transmission of HBV by active postexposure hepatitis B immunization in Chinese children.
对24名婴儿进行了研究,这些婴儿尽管接受了全程的血浆源性乙肝疫苗暴露后主动免疫,但乙肝病毒表面抗原(HBsAg)仍呈阳性。对血清样本中HBsAg常见中和表位“a”决定簇(核苷酸419 - 598)的聚合酶链反应扩增产物进行测序,并分析核苷酸突变情况。4例(16.7%)发生了导致124至147密码子之间氨基酸替换的突变。仅1例(N1)在密码子145处发生替换(从甘氨酸变为精氨酸,145R),另外3例在密码子126 - 129处。N1的母亲同时感染了野生型和突变型病毒。5年后,N1的血清仅显示野生型病毒。突变率与乙肝疫苗的抗-HBs反应之间无显著关系。结果表明,在没有免疫选择压力的情况下,145R变异体不常出现,且不稳定。“a”决定簇的突变并非中国儿童通过暴露后主动乙肝免疫未能预防母婴传播HBV的重要原因。