Altered antigenicity of 'a' determinant variants of hepatitis B virus.

Changes of hepatitis B surface antigen variants in carrier children before and after universal vaccination in taiwan

“…In addition, T126S and Q129H have also been shown to exhibit various degrees of altered binding of HBsAg to several monoclonal antibodies. 30 By studying the changes in hydrophilicity and conformation resulting from exchange of residues in the a determinant, amino acid substitutions in T126A, M133L, F134L, and T143M were found to have changes in the ␤ turn secondary structure. 31 The substitution of amino acid residues within the presumed second loop (residues 139-147) of a determinant may involve a change of the side chain of amino acid residues, for example, a loss of a negative charge in D144A mutant.…”

Licensed recombinant hepatitis B vaccines protect chimpanzees against infection with the prototype surface gene mutant of hepatitis B virus

“…Among a number of HBV variants with amino acid mutations in the a determinant, 2-31,72-77 those identified in relation to immunoprophylaxis, 2-27 coexisting anti-HBs, [28][29][30][31] or inability to detect HBsAg by several assays [72][73][74][75][76] may have weak avidity to anti-HBs, and several such variants have been demonstrated in vitro to have a reduced binding affinity for anti-HBs. 5,13,18,26,27,42,73 However, the protective immunity elicited by HB vaccines, which is usually polyclonal in nature, may not be totally lost or severely affected in vivo by the alteration of only a single amino acid in the conformation of the a epitope. The exact sequence recognized by neutralizing antibodies is still unknown.…”

“…Recent studies using peptide or yeast-expressed HBs antigens, together with detailed sequence analyses of HBV genotypes, 78 have suggested that in addition to Cys residues, several conserved residues are important for the conformation of the a epitope, i.e., Lys or Arg at codon 122, Thr at codon 123, 79,80 Lys at codon 141, Pro at codon 142, Asp at codon 144, and Gly at codon 145. [81][82][83][84] In this regard, it may be that among codon positions associated with amino acid substitutions, i.e., codon positions 120, 17,19,20,25,72 124, 21 126, 5,7,15,17,18,20,26,28,30,31 14,31,72,77 144, 7,16,17,[25][26][27]31,72 145, [2][3][4][5]7,11,12,[14][15][16]18,19,…”

“…3, 1999 genetic, or other unknown conditions of hosts may lead to inadequate or restricted immune responses to HBsAg. [68][69][70][71] The large number of reports of S gene mutants associated with unsuccessful perinatal immunoprophylaxis [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] has caused alarm that mutations of amino acids in the a determinant of HBsAg may be a significant cause of vaccine failure. However, molecular epidemiological data from Singapore, 7 Taiwan, 12,16 Indonesia, 14 England and Wales, 17 and the United States 48 have confirmed that, among cases of perinatal vaccine failure, the frequency of infection with S gene mutants is lower than that for infection with wild-type virus.…”

“…In the present study, the protective efficacy of licensed hepatitis B vaccines was evaluated against challenge with this mutant virus. There is evidence for the emergence of hepatitis B virus (HBV) mutants with amino acid substitutions in the a determinant of the surface (S) protein in individuals who received immunoprophylaxis against HBV either at birth [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] or during liver transplantation. [21][22][23][24][25][26][27] Also, such HBV mutants have been identified in chronic HBV carriers who acquired HBV infection naturally.…”