Molecular epidemiology of hepatitis B virus vaccine variants in Singapore

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

“…[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. Thus, it seems likely that many cases of perinatal vaccine failure are actually examples of vaccination failure not related to ''neutralization escape.''…”

“…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,…”

“…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.…”

Predictions of the emergence of vaccine-resistant hepatitis B in The Gambia using a mathematical model

“…Both the sexual and horizontal transmission of the variant is reduced by α, so k # l αk " and β # (i, j) l αβ " (i, j). The overall force of infection, λ g s (i, t), is modified by mutation as shown in equation (6). Matrices of the transmission coefficients β " (i, j) were calculated from the forces of infection using a particular ' who acquires infection from whom ' or WAIFW matrix [16] :…”

“…Hepatitis B virus (HBV) variants have been reported to arise in immunized individuals in three situations : (i) after liver transplantation, despite treatment with monoclonal antibodies against surface antigen (antiHBs) and hyper-immunoglobulin (HBIG) treatment [1][2][3], (ii) neonatal infections, despite HBIG and\or vaccination in the UK [4], Italy [5], Singapore [6], Indonesia [7] and Japan [8], and (iii) horizontal infections in young children despite vaccination in The Gambia [9]. The 22 nm subviral surface antigen peptides (HBsAg) used in the current vaccines (both plasma derived and recombinant) produce a narrower immune response than immunity following infection.…”