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A novel hepatitis B virus variant S 129 (Gln→Leu): Lack of correlation between antigenicity and immunogenicity
Author(s) -
Wu Li,
He JianWen,
Yao Xin,
Li HeMin,
Wen YuMei
Publication year - 1999
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/(sici)1096-9071(199912)59:4<424::aid-jmv2>3.0.co;2-l
Subject(s) - immunogenicity , antigenicity , virology , hepatitis a virus , virus , biology , epitope , medicine , antibody , immunology
A point mutation has been detected in the “a” determinant of hepatitis B surface antigen (HBsAg) in an infant immunised with hepatitis B vaccine after exposure to hepatitis B virus (HBV). This A‐to‐T point mutation at nucleotide 540 resulted in a glutamine‐to‐leucine substitution at amino acid residue 129 (129L). The S gene fragment (nucleotide 58–1072) of this isolate was cloned and used to substitute the wild‐type S gene in a plasmid (p3.8II), containing 1.2 copy of full‐length HBV genome with expression and replication efficiency. This plasmid p3.8II‐129L was used to transfect HepG2 cells. HBsAg expressed by p3.8II‐129L showed higher binding efficiency compared with the original plasmid containing the wild‐type clone. A panel of 24 anti‐HBs monoclonal antibodies (MAbs) was used to characterise the binding efficiency of HBsAg expressed by p3.8II‐129L. Eighteen showed higher binding to the antigen, whereas HBsAg expressed by p3.8II‐145R gave a consistently lower absorbance or were negative. Surprisingly, when the immunogenicity of plasmid constructs was used for DNA immunisation in Balb/c mice, the anti‐HBs response induced by p3.8II‐129L was significantly lower than that of the wild‐type p3.8II. The lack of correlation between the antigenicity profile (binding of expressed HBsAg to anti‐HBs in vitro), and the immunogenicity (induction of anti‐HBs by plasmid DNA in vivo) of HBsAg with leucine substitution at position 129 indicates that biological characteristics other than the binding efficiency of HBsAg to anti‐HBs could occur in HBsAg variants. These different aspects of the biological characteristics of S mutants merit further investigation. J. Med. Virol. 59:424–430, 1999. © 1999 Wiley‐Liss, Inc.