Vaccine-induced escape mutant of hepatitis B virus

Carman, William F.; Karayiannis, Peter; Waters, Jennifer A.; Thomas, Howard; Zanetti, Â.R.; Manzillo, G; Zuckerman, Arie J.

doi:10.1016/0140-6736(90)91874-a

Cited by 1,027 publications

(705 citation statements)

References 17 publications

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“…Some of the rare or unique changes (144 aspartic acid-alanine and 145 glycine-arginine) have also been found in newborns of carrier mothers who developed HBV infection despite prophylaxis with HBIG and vaccination. 7,[19][20][21] The glycine-to-arginine substitution at codon 145 has been shown to reduce binding to monoclonal as well as polyclonal anti-HBs. 9,11,13,22,23 In addition, synthetic peptides with a proline-to-serine substitution at codon 142, aspartic acid-to-alanine substitution at 144, and glycine-to-arginine substitution at 145 have been shown to have reduced binding to anti-HBs compared with wild-type HBsAg.…”

Section: Discussionmentioning

confidence: 99%

“…5,6 This region is conformational and is thought to consist of two loops held by disulfide bridges between cysteines 124 and 137, and cysteines 138 and 147. 7 The second loop is more conserved and confers most of the antigenicity of the 'a' determinant; this loop is sometimes referred to as the major hydrophilic region (MHR). HBV can be classified into four major subtypes: adr, adw, ayr, and ayw.…”

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confidence: 99%

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Hepatitis B virus S mutants in liver transplant recipients who were reinfected despite hepatitis B immune globulin prophylaxis†

Ghany¹,

Ayola²,

Villamil³

et al. 1998

Hepatology

307

225

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Early studies found that orthotopic liver transplantation (OLT) for hepatitis B virus (HBV)-related liver failure was associated with a very high rate of reinfection and severe and rapidly progressive liver disease, resulting in a significant decrease in graft and patient survival compared with patients transplanted for other causes of liver disease. 1,2 Various measures have been tried in an attempt to reduce the rate of reinfection. The most promising results have come from the use of long-term (Ն 6 months) high-dose hepatitis B immune globulin (HBIG). 3,4 However, this regimen is expensive, and a significant reduction in the rate of reinfection is mainly seen in patients who have nonreplicative infection pre-OLT. Reinfection despite HBIG immunoprophylaxis may be caused by inadequate neutralization of overwhelming amounts of wildtype HBV, or to breakthrough infection by immune escape mutants.The major B-cell epitopes of hepatitis B surface antigen (HBsAg) have been shown to reside in the 'a' determinant region located at amino acid positions 124-149. 5,6 This region is conformational and is thought to consist of two loops held by disulfide bridges between cysteines 124 and 137, and cysteines 138 and 147. 7 The second loop is more conserved and confers most of the antigenicity of the 'a' determinant; this loop is sometimes referred to as the major hydrophilic region (MHR). HBV can be classified into four major subtypes: adr, adw, ayr, and ayw. Antibodies to the 'a' determinant confer protection against all subtypes of HBV. 8 Mutations in the HBV S gene have been reported in OLT recipients who developed HBV reinfection despite prophylaxis with monoclonal or polyclonal hepatitis B surface antibody (anti-HBs). McMahon et al. found amino acid substitutions in the 'a' determinant in all three patients who were reinfected despite monoclonal anti-HBs prophylaxis, 9 while the incidence of mutations in the 'a' determinant in OLT recipients who were reinfected despite HBIG prophylaxis varied from 0% to 33%. 10-12 Some of these mutations, including the glycine-to-arginine substitution at codon 145, have been shown to decrease binding to monoclonal antiHBs, suggesting that the breakthrough infections were caused by immune escape mutants. 9,11,13 The number of patients cited in the above studies ranged from three to seven patients; therefore, the significance of S escape mutants in HBV reinfection post-OLT remains unclear. It is also possible that additional mutations may be present in the HBV S gene outside the 'a' determinant in patients who received polyclonal anti-HBs (HBIG). Unfortunately, there are very few data on the sequence in the rest of the S gene. In addition, to date, there are no data on the reversibility of these mutations after withdrawal of HBIG therapy.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Hepatitis B virus S mutants in liver transplant recipients who were reinfected despite hepatitis B immune globulin prophylaxis†

Ghany¹,

Ayola²,

Villamil³

et al. 1998

Hepatology

307

225

View full text Add to dashboard Cite

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“…As mentioned previously, the 'a' determinant is a highly conserved region of HBsAg, and contains the majority of epitopes that host anti-HBs antibodies will target. Mutations within the 'a' determinant have been observed in persons who have received the HBV vaccine in several regions of the world [4,[94][95][96]. The selective pressure may increase the emergence of surface mutants compared to wild-type.…”

Section: Global Usementioning

confidence: 99%

Serological and molecular epidemiological outcomes after two decades of universal infant hepatitis B virus (HBV) vaccination in Nunavut, Canada

Huynh¹,

Minuk

Uhanova

et al. 2017

Vaccine

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

2000

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SUMMARYVaccine escape variants of hepatitis B virus (HBV) have been identified world-wide. A mathematical model of HBV transmission is used to investigate the potential pattern of emergence of such variants. Attention is focused on The Gambia as a country with high quality epidemiological data, universal infant immunization and in which escape mutants after childhood infections have been observed. We predict that a variant cannot become dominant for at least 20 years from the start of vaccination, even when using a vaccine which affords no cross protection. The dominant factor responsible for this long time scale is the low rate of infectious contacts between infected and susceptible individuals (we estimate the basic reproduction number of hepatitis B in The Gambia to be 1n7). A variant strain that achieves high prevalence will also take many years to control, and it is questionable whether emergence will be identifiable by sero-surveillance until of high prevalence. The sensitivity of the model predictions to epidemiological and demographic factors is explored.

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Vaccine-induced escape mutant of hepatitis B virus

Cited by 1,027 publications

References 17 publications

Hepatitis B virus S mutants in liver transplant recipients who were reinfected despite hepatitis B immune globulin prophylaxis†

Hepatitis B virus S mutants in liver transplant recipients who were reinfected despite hepatitis B immune globulin prophylaxis†

Serological and molecular epidemiological outcomes after two decades of universal infant hepatitis B virus (HBV) vaccination in Nunavut, Canada

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

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