Mosaic hepatitis B virus core particles allow insertion of extended foreign protein segments

• Published in: Journal of general virology 1997-08, Vol.78 (8), p.2049-2053
• Main Authors: Koletzki, D, Zankl, A, Gelderblom, HR, Meisel, H, Dislers, A, Borisova, G, Pumpens, P, Kruger, DH, Ulrich, R
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Base Sequence; Cloning, Molecular - methods; Drug Design; Escherichia coli; Hantavirus - genetics; Hepatitis B Core Antigens - biosynthesis; Hepatitis B Core Antigens - ultrastructure; Hepatitis B virus - genetics; Microscopy, Electron; Mosaicism; Mutagenesis, Insertional - methods; Nucleocapsid - biosynthesis; Nucleocapsid - ultrastructure; Plasmids; Recombinant Fusion Proteins - biosynthesis; Recombinant Fusion Proteins - ultrastructure; Sequence Deletion; Vaccines, Synthetic; Viral Vaccines
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/0022-1317-78-8-2049

D Koletzki, A Zankl, HR Gelderblom, H Meisel, A Dislers, G Borisova, P Pumpens, DH Kruger and R Ulrich Institute of Medical Virology, Charite, Humboldt-University, Berlin, Germany. 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.