Vaccination of chronic hepatitis B virus carriers with preS2/S envelope protein is not associated with the emergence of envelope escape mutants

Soussan, Patrick Ben; Pol, Stanislas; Garreau, Florianne; Bréchot, Christian; Kremsdorf, Dina

doi:10.1099/0022-1317-82-2-367

Cited by 16 publications

(5 citation statements)

References 28 publications

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“…The presence of T118V and A128V were found significantly in HBV/D2, which concurs with our previous study [51] and hence are considered as signature residues of this subgenotype. Additional mutation outside the MHL region was also observed including the E164G mutation, which was earlier reported by another study on chronic HBV carriers [52] . However, its implication as a vaccine escape mutant is still unclear.…”

Section: Discussionsupporting

confidence: 76%

Molecular Characterization of HBV Strains Circulating among the Treatment-Naive HIV/HBV Co-Infected Patients of Eastern India

et al. 2014

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Previously we reported that the exposure to hepatitis B virus (HBV) infection serves as a major threat among the treatment naive HIV infected population of eastern India. Hence, molecular characterization of these strains is of utmost importance in order to identify clinically significant HBV mutations. A total of 85 treatment naive HIV/HBV co-infected participants were included of whom the complete basal core promoter/precore region, the core and the whole envelope gene could be successfully sequenced for 59, 57 and 39 isolates respectively. Following phylogenetic analysis, it was found that HBV/D was the predominant genotype with HBV/D2 (38.5%) being the most prevalent subgenotype followed by HBV/A1. The major mutations affecting HBeAg expression includes the A1762T/G1764A (13.6%), G1896A (22%) and G1862T mutation (33.9%) which was predominantly associated with HBV/A1. Moreover, the prevalence of G1896A was considerably high among the HBeAg negative HIV/HBV co-infected subjects compared to HBV mono-infection. The main amino acid substitutions within the MHC class II restricted T-cell epitope of HBcAg includes the T12S (15.8%) and T67N (12.3%) mutation and the V27I (10.5%) mutation in the MHC class I restricted T-cell epitope. PreS1/S2 deletion was detected in 3 isolates with all harboring the BCP double mutation. Furthermore, the frequently occurring mutations in the major hydrophilic loop of the S gene include the T125M, A128V and M133I/L. Therefore, this study is the first from India to report useful information on the molecular heterogeneity of the HBV strains circulating among the treatment naive HIV/HBV co-infected population and is thus clinically relevant.

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Section: Discussionsupporting

confidence: 76%

Molecular Characterization of HBV Strains Circulating among the Treatment-Naive HIV/HBV Co-Infected Patients of Eastern India

et al. 2014

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“…These include mutation V184A, previously detected in children vaccinated against HBV [Chong‐Jin et al, ] and in chronic HBV inactive carriers [Norouzi et al, ]. And also mutation E164G, previously identified in interferon responders, interferon treatment reverters [Gous et al, ], and in a vaccine non‐responder patients [Soussan et al, ]. In the pre‐S1 region, mutation F25L, which has been previously associated with HBsAg negativity in South African patients [Makondo et al, ], was identified in one HBsAg‐negative patient in this study.…”

Section: Discussionsupporting

confidence: 74%

Complete genome analysis of hepatitis B virus in human immunodeficiency virus infected and uninfected South Africans

Gededzha

Muzeze

Burnett

et al. 2016

Journal of Medical Virology

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Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections are highly endemic in South Africa. Data on the complete genome sequences of HBV in HIV-positive patients in South Africa are scanty. This study characterized the complete HBV genome isolated from both HIV-positive and negative patients at the Dr George Mukhari Academic Hospital (DGMAH), Pretoria. Serum samples from nine (five HIV-positive and four HIV-negative) patients attending the DGMAH from 2007 to 2011 were serologically tested, amplified, and sequenced for complete genome. Phylogenetic tree was constructed using MEGA6.0. Mutations were analyzed by comparing the sequences with genotype-matched GenBank references. Eight patients were HBsAg positive, with only one from the HIV positive group being negative. Phylogenetic analysis of the complete genome sequences classified them into five genotypes; A1 (n = 4), A2 (n = 1), C1 (n = 2), D1 (n = 1), and D3 (n = 1). Deletions up to 35 nucleotides in length were identified in this study. No drug resistance mutations were identified in the P ORF, while the L217R mutation was identified in one subgenotype A2 sequence. The double (A1762T/G1764A) and triple (T1753C/A1762T/G1764A) mutations in the Basal core promoter were identified in four and two sequences, respectively. In the core region, mutation G1888A was identified in four of the subgenotype A1 sequences. In conclusion, this study has added to the limited South African data on HBV genotypes and mutations in HBV/HIV co-infected and HBV mono-infected patients, based on complete HBV genome analysis. Subgenotype A1 was predominant, and no drug-resistant mutants were detected in the study. J. Med. Virol. 88:1560-1566, 2016. © 2016 Wiley Periodicals, Inc.

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“…For example, the preS-containing Hepacare vaccine was shown to stimulate stronger and more rapid cellular and humoral immune responses and to overcome anti-HBs non-responsiveness [153,154]. Other preS-containing HBs vaccine candidates demonstrated rapid seroprotection [155] and apparently prevented selection of the determinant a escape mutants [156].…”

Section: Prevention and Therapy Of Hepatitis B: A Potential Role For mentioning

confidence: 99%

Molecular Epidemiology and Immunology of Hepatitis B Virus Infection – An Update

2002

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Hepatitis B virus (HBV) continues to be one of the most important viral pathogens in humans. This review provides an update on the molecular epidemiology and immunology of HBV infection. DNA sequencing has allowed replacement of the initial serotypic classification of HBV strains by a more systematic genotype system that currently consists of 7 members (genotypes A–G). More recently, sequence analysis of virus isolates from many individual patients has revealed the occurrence of certain mutational hot spots in the genome, some of which appear to correlate with the patient’s immunological and/or disease status; however, cause and effect are not always easily discernible. This holds particularly for the issue of whether virus variants exist that have, per se, an increased pathogenic potential; due to the scarcity of appropriate experimental in vivo models, such hypotheses are difficult to prove. Similarly, because of the compact organization of the HBV genome, almost every single mutation may have pleiotropic phenotypic effects. Nonetheless, there is accumulating evidence that at least some frequently observed mutations are causally related to viral escape from selective pressures, such as the presence of antibodies against dominant B cell epitopes, or drugs that inhibit the viral reverse transcriptase; possibly, this is also true for the cellular immune response. Therefore, despite the availability of an effective prophylactic vaccine, further extensive efforts are required to monitor the emergence of vaccination- and therapy-resistant HBV variants and to prevent their spread in the general population.

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Vaccination of chronic hepatitis B virus carriers with preS2/S envelope protein is not associated with the emergence of envelope escape mutants

Cited by 16 publications

References 28 publications

Molecular Characterization of HBV Strains Circulating among the Treatment-Naive HIV/HBV Co-Infected Patients of Eastern India

Molecular Characterization of HBV Strains Circulating among the Treatment-Naive HIV/HBV Co-Infected Patients of Eastern India

Complete genome analysis of hepatitis B virus in human immunodeficiency virus infected and uninfected South Africans

Molecular Epidemiology and Immunology of Hepatitis B Virus Infection – An Update

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