A novel hepatitis B virus variant S 129 (Gln-->Leu): lack of correlation between antigenicity and immunogenicity.
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.
Wu
L
L
Department of Molecular Virology, Shanghai Medical University, Shanghai, P.R. China.
He
J W
JW
Yao
X
X
Li
H M
HM
Wen
Y M
YM
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D005814:Genes, Viral; D006508:Hepatitis Antibodies / Q000097:blood; D006509:Hepatitis B / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D017325:Hepatitis B Vaccines / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000235:genetics / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D017354:Point Mutation; D017422:Sequence Analysis, DNA; D014162:Transfection; D019444:Vaccines, DNA / Q000276:immunology
D006508:Hepatitis Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D006513:Hepatitis B e Antigens; D019444:Vaccines, DNA