Hepatitis B surface antigen variants in vaccinees, blood donors and an interferon‐treated patient

Abstract

Variants of hepatitis B virus (HBV), with amino acid substitutions in the major antigenic "a" determinant of hepatitis B surface antigen (HBsAg), have been described mainly in vaccinated children. In the present study in addition to vaccinated children, we have investigated Chinese blood donors positive for anti-HBc alone, and a patient with continuing liver disease after interferon-induced seroconversion to anti-HBs. Variants were detected in two of four children with break-through infections. One child had a double mutation (P142S and G145R) and the other a G145A substitution. Three of seven anti-HBc positive Chinese blood donors had a T131I substitution, whilst the interferon-treated patient had a treble amino acid substitution (P142S, G145R and N146D). The present results indicate that HBsAg variants may exist in individuals other than vaccinated children.

Frequency of hepatitis B virus ‘a’ determinant variants in unselected Spanish chronic carriers

“…Five amino acid positions were involved, mainly 129 (6 mutants), 145 (5 mutants), and 126 (4 mutants). The most frequent substitutions were Gln129His (5 strains) [Oon et al, 1996] and Gly145Ala (4 strains) [Seddigh-Tonekaboni et al, 2001]. However, only a single mutant 145Arg was found.…”

“…Amino-acid changes that have been reported to be associated with vaccine escape were found in samples from 18 patients (6.6%). The findings involved positions 120, 126, 129, 144, and 145, and included the following substitutions: Pro120Ser [ChongJin et al, 1999] (n ¼ 1); Thr126Ala [Carman, 1997] (n ¼ 1); Thr126Ile (genotype D) [Carman, 1997] (n ¼ 1); Thr126Asn [He et al, 2001] (n ¼ 1); Thr126Ser [He et al, 2001] (n ¼ 1); Gln129His [Carman, 1997] (n ¼ 5); Gln129Arg [Ho et al, 1998](n ¼ 1); Asp144Ala [Oon et al, 1996] (n ¼ 2); Gly145Arg [Carman, 1997;Lee et al, 2001;Seddigh-Tonekaboni et al, 2001] (n ¼ 1); and Gly145Ala [Seddigh-Tonekaboni et al, 2001] (n ¼ 4).…”

“…Such mutants have also been reported in association with escape from vaccineinduced immunity [Oon et al, 1995;Carman, 1997;Ho et al, 1998;Chong-Jin et al, 1999;He et al, 2001;Lee et al, 2001;Seddigh-Tonekaboni et al, 2001] and with failures of therapy with specific immunoglobulin in newborns from carrier women and in liver-transplant recipients [Harrison et al, 1994;Oon et al, 1996Oon et al, , 2002Brind et al, 1997;Carman, 1997;Ngui et al, 1997;Protzer-Knolle et al, 1998;Santantonio et al, 1999;Roznovsky et al, 2000;Liu et al, 2002]. The amino-acid substitution Gly145Arg has been reported most frequently [Francois et al, 2001], and is known to be stable [Zuckerman and Zuckerman, 1999].…”

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

“…Alterations of the structure of HBsAg can disrupt the binding ability of polyclonal antibodies to it, because they contain several epitopes for T or B cells. The S mutants emerge during chronic HBV infections, often in patients treated with interferon and may represent the way by which the virus overcomes host immune responses (Roznovsky et al, 2000;Seddigh-Tonekaboni et al, 2001;Wakil et al, 2002). As shown in Table 2, the present amino acids HBV/D11isolates to sure that subgenotype should harbor nucleotide and amino acid motifs which are specific to novel subgenotype.…”

HBsAg Variants: Common Escape Issues

“…These variants are summarized in Figure 1 and Table 1. In many studies, mutations in vaccinated children were preferentially located in the "a" determinant (11,12), in contrast to the more randomly located mutations in unvaccinated children (13,14). In general, replacement in the presumed second "a" determinant loop, including aa positions 144 and 145, are more often associated with anti-HBs immune pressure, than mutations in other epitopic domains of the MHR (Figure 1) (5).…”