Mutations in the envelope gene of hepatitis B virus variants co-occurring with antibody to surface antigen in sera from patients with chronic hepatitis B

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

“…Our results do not address the issue of other HBV S gene mutants. 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.…”

“…[21][22][23][24][25][26][27] Also, such HBV mutants have been identified in chronic HBV carriers who acquired HBV infection naturally. [28][29][30][31] Because the a determinant of the HBV S protein is believed to contain a major neutralization epitope of HBV, it has been postulated that S gene mutants are generated by immune pressure and that they may spread among vaccinated individuals.…”

Identification of Novel D11 Hepatitis B Surface Antigen Subgenotype in Jeddah, Kingdom of Saudi Arabia

“…Sense mutation of nucleotides may lead to changes in the amino acid sequence either by substitution, insertion or deletion (Weinberger et al, 2000), otherwise establishment of nonsense mutations does not cause any change in the amino acid sequence (Rodriguez-Frias et al, 1999;Thuy et al, 2005). Sense mutations can lead to the creation of escape mutants which can alter group-specific antigenicity (Kohno et al, 1996;Miyake et al, 1996;Kfoury Baz et al, 2011). It can disrupt the antigenicity of HBsAg by modifying amino acids directly involved in expression of the antigen (Rodriguez-Frias et al, 1999).…”

HBsAg Variants: Common Escape Issues

“…A number of escape-variant viruses during the course of chronic infection within the "a" determinant were reported to be replicated in spite of the presence of antiHBs (15,39,(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68). This phenomenon, which has been explored by molecular approaches in vaccinated individuals, may result from at least seven reasons.…”

“…These "a" determinant variants may go undetected by conventional HBsAg screening tests. Sixth, the anti-HBs in these patients may possibly be directed against the epitopes outside the "a" determinant, such as d/y or w/r subtype determinants (66). Seventh, low expression of HBsAg due to a low viral load (which might be just enough for viral assembly, but underneath the sensitivity of standard tests) thus moving it below the sensitivity of standard serologic assays (69).…”