Properties of modified hepatitis B virus surface antigen particles carrying preS epitopes

Prange, Reinhild; Werr, Margaret; Birkner, Matthias; Hilfrich, Ralf; Streeck, Rolf E.

doi:10.1099/0022-1317-76-9-2131

Cited by 22 publications

(8 citation statements)

References 36 publications

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“…Our data suggest that the "a" determinants on the WHsAg are quite different. Our data confirm the importance of anti-pre-S2 Abs, which has been suggested before (15,16,28). This supports the notion that a new generation of anti-HBV vaccine should contain this epitope.…”

Section: Discussionsupporting

confidence: 92%

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Targeting Murine Immune Responses to Selected T Cell- or Antibody-Defined Determinants of the Hepatitis B Surface Antigen by Plasmid DNA Vaccines Encoding Chimeric Antigen

Schirmbeck

Zheng²,

Roggendorf³

et al. 2001

The Journal of Immunology

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By exchanging sequences from the middle-surface (MS) and small-surface (S) Ag of hepatitis B virus (HBV) with corresponding sequences of the MS Ag of woodchuck hepatitis virus, we constructed chimeric MS variants. Using these constructs as DNA vaccines in mice, we selectively primed highly specific (non-cross-reactive) Ab responses to pre-S2 of the HBV MS Ag and the “a” determinant of the HBV S Ag, as well as Ld- or Kb-restricted CTL responses to HBV S epitopes. In transgenic mice that constitutively express large amounts of HBV surface Ag in the liver we could successfully suppress serum antigenemia (but not Ag production in the liver) by adoptive transfer of anti-pre-S2 or anti-“a” immunity but not CTL immunity. DNA vaccines greatly facilitate construction of chimeric fusion Ags that efficiently prime specific, high-affinity Ab and CTL responses. Such vaccines, in which sequences of an Ag of interest are exchanged between different but related viruses, are interesting tools for focusing humoral or cellular immunity on selected antigenic determinants and elucidating their biological role.

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Section: Discussionsupporting

confidence: 92%

“…1A). Most human and murine anti-S Abs bind to the conformational "a" determinant located at the S 120 -147 region (1,(15)(16)(17). In H-2 d and H-2 b mice, Ab responses but not CTL responses are readily primed against determinants in the pre-S2 domain of HBsAg (11).…”

Section: Construction Of Chimeric Ms Ags Of Hbv and Whvmentioning

confidence: 99%

Targeting Murine Immune Responses to Selected T Cell- or Antibody-Defined Determinants of the Hepatitis B Surface Antigen by Plasmid DNA Vaccines Encoding Chimeric Antigen

Schirmbeck

Zheng²,

Roggendorf³

et al. 2001

The Journal of Immunology

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“…A natural HBV point mutant unable to express the M protein was isolated from a patient and demonstrated that this protein is not required [125] , whereas suppression of L or S expression impeded virion formation [122,123] . An L construct with an N-terminally fused secretion signal g enerating only the e-preS conformation was secreted as a component of subviral particles [126] but failed to support virion formation [58] . Apparently, the i-preS conformation of L exposing the preS domain at the cytosolic side of the ER was essential for nucleocapsid envelopment.…”

Section: Formationmentioning

confidence: 99%

Hepatitis B virus morphogenesis

Bruss

2007

WJG

242

252

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The hepatitis B virus (HBV) particle consists of an envelope containing three related surface proteins and probably lipid and an icosahedral nucleocapsid of approximately 30 nm diameter enclosing the viral DNA genome and DNA polymerase. The capsid is formed in the cytosol of the infected cell during packaging of an RNA pregenome replication complex by multiple copies of a 21-kDa C protein. The capsid gains the ability to bud during synthesis of the viral DNA genome by reverse transcription of the pregenome in the lumen of the particle. The three envelope proteins S, M, and L shape a complex transmembrane fold at the endoplasmic reticulum, and form disulfide-linked homoand heterodimers. The transmembrane topology of a fraction of the large envelope protein L changes posttranslationally, therefore, the N terminal domain of L (preS) finally appears on both sides of the membrane. During budding at an intracellular membrane, a short linear domain in the cytosolic preS region interacts with binding sites on the capsid surface. The virions are subsequently secreted into the blood. In addition, the surface proteins can bud in the absence of capsids and form subviral lipoprotein particles of 20 nm diameter which are also secreted.

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“…The intracellular LS protein with additional preS1 and preS2 domains N-terminal to the S region is expressed as nonglycosylated p39 and glycosylated gp42 (3). All three HBsAg species form particulate structures when expressed individually (2)(3)(4). The MS and S Ags are efficiently secreted from transfected cells, whereas the LS Ag is exclusively found intracellularly (3).…”

mentioning

confidence: 99%

“…Hepatitis B surface Ag (HBsAg) 4 secreted by HBV-infected hepatocytes and present in the plasma of infected individuals is a complex macromolecule composed of proteins and lipids (1,2). The 22-nm coreless HBsAg lipoprotein particles contain three natural variants of HBsAg designated large (LS), middle (MS), and small (S) surface proteins.…”

mentioning

confidence: 99%

Priming Biologically Active Antibody Responses Against an Isolated, Conformational Viral Epitope by DNA Vaccination

Riedl

Kholy

Reimann

et al. 2002

The Journal of Immunology

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The immunodominant, conformational “a” determinant of hepatitis B surface Ag (HBsAg) elicits Ab responses. We selectively expressed the Ab-binding, glycosylated, native a determinant (residue 120–147) of HBsAg in a fusion protein containing C-terminally the HBsAg fragment SII (residue 80–180) fused to a SV40 T-Ag-derived hsp73-binding 77 aa (T77) or non-hsp-binding 60 aa (T60) N terminus. A DNA vaccine encoding non-hsp-binding secreted T60-SII fusion protein-stimulated murine Ab responses with a similar efficacy as a DNA vaccine encoding the secreted, native, small HBsAg. A DNA vaccine encoding hsp73-binding, intracellular T77-SII fusion protein-stimulated murine Ab responses less efficiently but comparable to a DNA vaccine encoding the intracellular, native, large HBsAg. HBsAg-specific Abs elicited by either the T60-SII-expressing or the T77-SII-expressing DNA vaccine suppressed HBsAg antigenemia in transgenic mice that produce HBsAg from a transgene in the liver; hence, a biologically active B cell response cross-reacting with the native, viral envelope epitope was primed by both DNA vaccine constructs. HBsAg-specific Ab and CTL responses were coprimed when an S20–50 fragment (containing the immunodominant, Ld-binding epitope S28–39) of HBsAg was fused C-terminally to the pCI/T77-SII sequence (pCI/T77-SII-Ld DNA vaccine). Chimeric, polyepitope DNA vaccines encoding conformational, Ab-binding epitopes and MHC class I-binding epitopes can thus efficiently deliver antigenic information to different compartments of the immune system in an immunogenic way.

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Properties of modified hepatitis B virus surface antigen particles carrying preS epitopes

Cited by 22 publications

References 36 publications

Targeting Murine Immune Responses to Selected T Cell- or Antibody-Defined Determinants of the Hepatitis B Surface Antigen by Plasmid DNA Vaccines Encoding Chimeric Antigen

Targeting Murine Immune Responses to Selected T Cell- or Antibody-Defined Determinants of the Hepatitis B Surface Antigen by Plasmid DNA Vaccines Encoding Chimeric Antigen

Hepatitis B virus morphogenesis

Priming Biologically Active Antibody Responses Against an Isolated, Conformational Viral Epitope by DNA Vaccination

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