title: Mosaic hepatitis B virus core particles allow insertion of extended foreign protein segments.
abstract: Because of its particular immunological properties, the core protein of hepatitis B virus (HBcAg) has become one of the favoured 'virus-like particles' for use as a carrier of foreign epitopes. A new strategy to construct core particles presenting extended foreign protein segments was established based on the introduction of a linker containing a translational stop codon between sequences encoding a C-terminally truncated HBcAg (HBcAg delta) and a foreign protein sequence. Expression in an Escherichia coli suppressor strain allowed the simultaneous synthesis of both HBcAg delta and a read-through fusion protein containing a part of the hantavirus nucleocapsid protein. After purification, the presence of core-like mosaic particles with HBc and hantavirus antigenicity was demonstrated by electron microscopy and immunological tests. This strategy of partial stop codon suppression should improve the use of HBcAg as a carrier of foreign epitopes by allowing insertion of long foreign sequences into particle-forming proteins. The resulting mosaic particles should be of general interest for further vaccine developments.
authors.affiliation: Institute of Medical Virology, Charité, Humboldt-University, Berlin, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Koletzki
authors.forename: A
authors.initials: A
authors.lastname: Zankl
authors.forename: H R
authors.initials: HR
authors.lastname: Gelderblom
authors.forename: H
authors.initials: H
authors.lastname: Meisel
authors.forename: A
authors.initials: A
authors.lastname: Dislers
authors.forename: G
authors.initials: G
authors.lastname: Borisova
authors.forename: P
authors.initials: P
authors.lastname: Pumpens
authors.forename: D H
authors.initials: DH
authors.lastname: Krüger
authors.forename: R
authors.initials: R
authors.lastname: Ulrich
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular / Q000379:methods*; D015195:Drug Design; D004926:Escherichia coli; D006476:Orthohantavirus / Q000235:genetics*; D006512:Hepatitis B Core Antigens / Q000096:biosynthesis* / Q000648:ultrastructure; D006515:Hepatitis B virus / Q000235:genetics*; D008854:Microscopy, Electron; D009030:Mosaicism; D016254:Mutagenesis, Insertional / Q000379:methods*; D019251:Nucleocapsid / Q000096:biosynthesis* / Q000648:ultrastructure; D010957:Plasmids; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000648:ultrastructure; D017384:Sequence Deletion; D014614:Vaccines, Synthetic; D014765:Viral Vaccines
chemical_list: D006512:Hepatitis B Core Antigens; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D014765:Viral Vaccines