Analysis of foreign epitope inserts in HBcAg. Approaches to solving the problem of core particle self-assembly

The hepatitis B virus core antigen (HBcAg) is a promising protein carrier f or exposing the epitopes of various human and animal pathogens. HBcAg-based chimeric proteins can be used in creating highly efficient vaccines; howev er, not all chimeric HBcAg with foreign epitope inserts are capable of asse mbly into virus-like particles. Using computer programs ProAnalyst, SALIX, and QSARPro, we examined the relationship between the self-assembly capabil ity of chimeric HBcAg and the physicochemical properties of the inserts. Th e self-assembly was found to be impaired when the inserted peptides contain ed highly hydrophobic and bulky residues tending to form beta-structures; t his especially concerned the C-proximal residues in the insert. Recommendat ions were elaborated for constructing foreign epitopes that would ensure co rrect self-assembly of chimeric HBcAg particles.