Molecular Variants of Hepatitis B Surface Antigen (HBsAg)

Jazayeri, Seyed Mohammad; Alavian, Seyed Moayed; Dindoost, Payam; Thomas, Howard; Karayiannis, Peter

doi:10.1002/9781118637272.ch8

Cited by 4 publications

(3 citation statements)

References 192 publications

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“…Most of the mutations found in the upstream and downstream region of the HBsAg “a” determinant were responsible for vaccine breakthroughs that tended to cluster within known Th and/or CTL epitopes [62]. In addition, several groups predicted the secondary structure of HBsAg with at least four different transmembrane domains, but the amino acid positions and the numbers within these domains were flexible [11, 53, 60, 63].…”

Section: Discussionmentioning

confidence: 99%

“…Perhaps, due to the above, mutations found at these positions had no effect on the reactivity of HBsAg in commercial diagnostic assays (Fig 5A and 5B). Amino acid residues 206–215 of HBsAg contained an antigenic epitope specific for MHC class I T- cells (CD8) and vaccine-induced mutations such as 213M/F/I have been found within this region [62, 64]. L213 was found in the endoplasmic lumen adjacent to the C-terminus of the HBs amino acid sequence according to the predicted secondary structure.…”

Section: Discussionmentioning

confidence: 99%

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Investigation of a Novel Hepatitis B Virus Surface Antigen (HBsAg) Escape Mutant Affecting Immunogenicity

Hossain

Ueda

2017

PLoS ONE

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Mutation in the hepatitis B virus surface antigen (HBsAg) may affect the efficiency of diagnostic immunoassays or success of vaccinations using HBsAg. Thus, antigenicity and immunogenicity analyses of the mutated HBsAg are necessary to develop novel diagnostic tools and efficient vaccinations. Here, the in vitro antigenicity of three wild-type HBsAg open reading frames (ORFs) (adr4, W1S [subtype adr] and W3S [subtype adr]) isolated from clinically infected patients and nineteen synthesized single/double/multiple amino acid-substituted mutants were tested with commercial ELISA kits. Immunofluorescence staining of transfected cells and Western blot analysis confirmed that these ORFs were expressed at comparable levels in HEK-293 cells. W1S and adr4 were clearly detected, whereas W3S could not be detected. Using the same commercial immunoassay kit, we found that the single mutants, K120P and D123T, were marginally reactive, whereas W3S-aW1S and the double mutant, K120P/D123T, exhibited antigenicity roughly equivalent to the wild-type wako1S. On the other hand, the single mutants of W1S, P120K and T123D, significantly impaired the reactivity, while W1S-aW3S and the double mutant of W1S, P120K/T123D, resulted in a complete loss of antigenicity. In addition, ELISA revealed reduced HBs antigenicity of two mutants, W1S N146G and W1S Q129R/G145R. These commercial ELISA-based antigenic reactivities of HBsAg were also strongly correlated with the predicted Ai alterations of affected amino acids due to the specific mutation. In conclusion, this study showed for the first time that lysine (K120) and aspartate (D123) simultaneously affected HBsAg antigenicity, leading to diagnostic failure. These findings will improve diagnostic assays and vaccine development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Investigation of a Novel Hepatitis B Virus Surface Antigen (HBsAg) Escape Mutant Affecting Immunogenicity

Hossain

Ueda

2017

PLoS ONE

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“…HBsAgS SVPs share important immunological determinants with the mature virus, and therefore, SVPs derived from patient serum or recombinant SVPs represent effective immunogens for the induction of a protective immune response [26][27][28]. Vaccinated individuals develop antibodies targeting the "a"-determinant region, which provides protection against the infection of all HBV serotypes [20,29]. The discovery and characterization of "empty" genome-free virions containing HBsAg and capsid is reviewed by Hu and Liu, 2017 [30].…”

Section: Introductionmentioning

confidence: 99%

Hepatitis B Virus (HBV) Subviral Particles as Protective Vaccines and Vaccine Platforms

Jeevan-Raj

Netter

2020

Viruses

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Hepatitis B remains one of the major global health problems more than 40 years after the identification of human hepatitis B virus (HBV) as the causative agent. A critical turning point in combating this virus was the development of a preventative vaccine composed of the HBV surface (envelope) protein (HBsAg) to reduce the risk of new infections. The isolation of HBsAg sub-viral particles (SVPs) from the blood of asymptomatic HBV carriers as antigens for the first-generation vaccines, followed by the development of recombinant HBsAg SVPs produced in yeast as the antigenic components of the second-generation vaccines, represent landmark advancements in biotechnology and medicine. The ability of the HBsAg SVPs to accept and present foreign antigenic sequences provides the basis of a chimeric particulate delivery platform, and resulted in the development of a vaccine against malaria (RTS,S/AS01, MosquirixTM), and various preclinical vaccine candidates to overcome infectious diseases for which there are no effective vaccines. Biomedical modifications of the HBsAg subunits allowed the identification of strategies to enhance the HBsAg SVP immunogenicity to build potent vaccines for preventative and possibly therapeutic applications. The review provides an overview of the formation and assembly of the HBsAg SVPs and highlights the utilization of the particles in key effective vaccines.

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Clearance of HBV DNA in immunized children born to HBsAg‐positive mothers, years after being diagnosed with occult HBV infection

Sadeghi

Yahyapour

Poortahmasebi

et al. 2015

Journal of Viral Hepatitis

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In a previous study, we observed immunoprophylaxis failure due to occult hepatitis B virus (HBV) infection (OBI) despite the presence of adequate levels of anti-HBs in 21 (28%) of 75 children born to HBsAg-positive mothers. The aim of the study was to explore the maintenance of this cryptic condition in this population. Of 21 OBI-positive children, 17 were enrolled. HBV serological profiles were determined by enzyme-linked immunosorbent assay. Highly sensitive real-time and standard PCR followed by direct sequencing were applied in positive cases. The mean age (±SD) of studied patients was 6.57 ± 2.75 years. All children still were negative for HBsAg. All but one (94%) were negative for HBV DNA. Only two children were positive for anti-HBc. The results of the most recent anti-HBs titration showed that 4 (23.5%) and 13 (76.5%) had low (<10 IU/mL) and adequate (>10 IU/mL) levels of anti-HBs, respectively. The only still OBI-positive patient had an HBV DNA level of 50 copy/mL, carried the G145R mutation when tested in 2009 and again in 2013 in the 'a' determinant region of the surface protein. Further follow-up showed that after 18 months, he was negative for HBV DNA. In high-risk children, the initial HBV DNA positivity early in the life (vertical infection) does not necessarily indicate a prolonged persistence of HBV DNA (occult infection). Adequate levels of anti-HBs after vaccine and hepatitis B immune globulin immunoprophylaxis following birth could eventually clear the virus as time goes by. Periodic monitoring of these children at certain time intervals is highly recommended.

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Molecular Variants of Hepatitis B Surface Antigen (HBsAg)

Cited by 4 publications

References 192 publications

Investigation of a Novel Hepatitis B Virus Surface Antigen (HBsAg) Escape Mutant Affecting Immunogenicity

Investigation of a Novel Hepatitis B Virus Surface Antigen (HBsAg) Escape Mutant Affecting Immunogenicity

Hepatitis B Virus (HBV) Subviral Particles as Protective Vaccines and Vaccine Platforms

Clearance of HBV DNA in immunized children born to HBsAg‐positive mothers, years after being diagnosed with occult HBV infection

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