Modulation of the immunogenicity of virus-like particles composed of mutant hepatitis B virus envelope subunits

Characterization of the disassembly and reassembly of the HBV glycoprotein surface antigen, a pliable nanoparticle vaccine platform

“…Some sAg cysteines cannot be mutated and are essential for secretion of sAg particles and antigenicity (32, 33), while other cysteines can be mutated to alanine without affecting particle formation. Still, those constructs containing cysteine to alanine mutations were found to be less immunogenic (40). Our analysis of sAg particles indicated that the level of disulfide bond formation varied depending on the expression system, and was heterogeneous among sAg particles.…”

Modification of Asparagine-Linked Glycan Density for the Design of Hepatitis B Virus Virus-Like Particles with Enhanced Immunogenicity

“…6D). Cytotoxic T lymphocyte (CTL) activity was measured at two different time points, 1 and 4 weeks after immunization of BALB/c mice with the different VLP types resulting in CTL responses, which were not significantly different (data not shown), indicating that the cellular immune response against HBsAgS VLPs is possibly dictated by protease sensitivity and antigen processing (34).…”

“…The analysis of 1556 HBsAgS-specific DNA sequences extracted from a HBV database (SeqHepB) (34,62) revealed that asparagine at position 116 or 130 is present in Ͻ1% of the naturally occurring sequences. The amino acids threonine at position 116 and glycine at position 130 are conserved in 99.5% and 98% of the analyzed sequences, respectively.…”

“…In an attempt to enhance the VLP immunogenicity, biochemically modified VLPs were generated with a reduced level of disulfide bonding to weaken the particulate structure and to promote antigen processing (34). The modification of the disulfide bonding pattern possibly influences antigen processing and epitope selection via the MHC class II pathway (35,36).…”

Toward the development of monoclonal antibody-based assays to probe virion-like epitopes in hepatitis B vaccine antigen

“…As reported recently, comparative immunization studies indicated that changes in the disulfide bonding pattern modulate the HBsAg VLP immunogenicity most likely due to structural changes. 20 To probe changes in immune reactivity due to structural perturbation, this study took advantage of the disulfide-dependent nature of MHR conformation in HBsAg. By fully reducing all the disulfides with DTT during plate coating, the changes in mAb binding activity to surface immobilized HBsAg were assessed.…”