1887

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 (HBcAgA) and a foreign protein sequence. Expression in an suppressor strain allowed the simultaneous synthesis of both HBcAgA 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.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-78-8-2049
1997-08-01
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/78/8/9267006.html?itemId=/content/journal/jgv/10.1099/0022-1317-78-8-2049&mimeType=html&fmt=ahah

References

  1. Borisova G. P., Berzins I., Pushko P. M., Pumpen P., Gren E. J., Tsibinogin V. V., Loseva V., Ose V., Ulrich R., Siakkou H., Rosenthal H. A. 1989; Recombinant core particles of hepatitis B virus exposing foreign antigenic determinants on their surface. FEBS Letters 259:121–124
    [Google Scholar]
  2. Borisova G., Arya B., Dislers A., Borschukova O., Tsibinogin V., Skrastina D., Eldarov M. A., Pumpens P., Skryabin K. G., Grens E. 1993; Hybrid hepatitis B virus nucleocapsid bearing an immunodominant region from hepatitis B virus surface antigen. Journal of Virology 67:3696–3701
    [Google Scholar]
  3. Clarke B. E., Newton S. E., Carroll A. R., Francis M. J., Appleyard G., Syred A., Highfield P. E., Rowlands D. J., Brown F. 1987; Improved immunogenicity of a peptide epitope after fusion to hepatitis B core protein. Nature 330:381–384
    [Google Scholar]
  4. Gallina A., Bonelli F., Zentilin L., Rindi G., Muttini M., Milanesi G. 1989; A recombinant hepatitis B core antigen polypeptide with the protamine-like domain deleted self-assembles into capsid particles but fails to bind nucleic acids. Journal of Virology 63:4645–4652
    [Google Scholar]
  5. Gelderblom H., Bauer H., Frank H., Wigand R. 1967; The structure ofgroup II adenoviruses. JournalofGeneral Virology 1:553–560
    [Google Scholar]
  6. Hirashima A., Harigari H., Watanabe I. 1979; Enhancing effect of magnesium ion on cell-free synthesis of read-through protein of bacteriophage Qβ . Biochemical and Biophysical Research Communications 88:1046–1051
    [Google Scholar]
  7. Isaguliants M. G., Kadoshnikov Yu. P., Kalinina T. I., Khudyakov Yu. E., Semiletov Yu. A., Smirnov V. D., Wahren B. 1996; Expression of HIV-1 epitopes inserted into the nucleocapsid protein of human hepatitis B virus. Biochemistry (Moscow) 61:393–403
    [Google Scholar]
  8. Lomonossoff G. P., Johnson J. E. 1995; Viral expression systems for peptides. Seminars in Virology 6:257–267
    [Google Scholar]
  9. Lundkvist A., Niklasson B. 1994; Hemorrhagic fever with renal syndrome and other hantavirus infections. Reviews in Medical Virology 4:177–184
    [Google Scholar]
  10. Lundkvist A., Fatouros A., Niklasson B. 1991; Antigenic variation of European haemorrhagic fever with renal syndrome virus strains characterized using bank vole monoclonal antibodies. Journal of General Virology 72:2097–2103
    [Google Scholar]
  11. Lundkvist A., Kallio-Kokko H., Brus Sjölander K., Lankinen H., Niklasson B., Vaheri A., Vapalahti O. 1996; Characterization of Puumala virus nucleocapsid protein: identification of B-cell epitopes and domains involved in protective immunity. Virology 216:397–406
    [Google Scholar]
  12. Milich D. R., McLachlan A., Moriarty A., Thornton G. B. 1987; Immune response to hepatitis B virus core antigen (HBcAg): localization of T cell recognition sites within HBcAg/HBeAg. Journal of Immunology 139:1223–1231
    [Google Scholar]
  13. Pumpens P., Borisova G. P., Crowther R. A., Grens E. 1995; Hepatitis B virus core particles as epitope carriers. Intervirology 38:63–74
    [Google Scholar]
  14. Reip A., Haring B., Sibold C., Stohwasser R., Bautz E. K. F., Darai G., Meisel H., Krüger D. H. 1995; Coding strategy of the S and M genomic segments of a hantavirus representing a new subtype of the Puumala serotype. Archives of Virology 140:2011–2026
    [Google Scholar]
  15. Schmaljohn C. 1994; Prospects for vaccines to control viruses in the family Bunyaviridae. Reviews in Medical Virology 4:185–196
    [Google Scholar]
  16. Schödel F., Milich D. R., Will H. 1990; Hepatitis B virus nucleocapsid/pre-S2 fusion proteins expressed in attenuated Salmonella for oral vaccination. Journal of Immunology 145:4317–4321
    [Google Scholar]
  17. Schödel F., Kelly S., Tinge S., Hopkins S., Peterson D., Milich D., Curtiss R. III 1996; Hybrid hepatitis B virus core antigen as a vaccine carrier moiety. II Expression in avirulent Salmonella spp. for mucosal immunization. In Novel Strategies in Design and Production of Vaccines pp. 15–22 Cohen S., Shafferman A. Edited by New York: Plenum Press;
    [Google Scholar]
  18. Smiley B. K., Minion F. C. 1993; Enhanced readthrough of opal (UGA) stop codons and production of Mycoplasma pneumoniae P1 epitopes in Escherichia coli . Gene 134:33–40
    [Google Scholar]
  19. Stahl S. J., Murray K. 1989; Immunogenicity of peptide fusions to hepatitis B virus core antigen. Proceedings of the National Academy of Sciences, USA 86:6283–6287
    [Google Scholar]
  20. Ulrich R., Borisova G. P., Gren E., Berzin I., Pumpen P., Eckert R., Ose V., Siakkou H., Gren E. J., von Baehr R., Krüger D. H. 1992; Immunogenicity of recombinant core particles of hepatitis virus containing epitopes of human immunodeficiency virus 1 core antigen. Archives of Virology 126:321–328
    [Google Scholar]
  21. Ulrich R., Gerlich W. H., Krüger D. H. 1996; Chimaera and its modern virus-like descendants. Intervirology 39:126–132
    [Google Scholar]
  22. Ulrich R., Nassal M., Meisel H., Krüger D. H. 1997; Core particles of hepatitis B virus as carrier for foreign epitopes. Advances in Virus Research in press
    [Google Scholar]
  23. von Brunn A., Brand M., Reichhuber Ch., Morys-Wortmann C., Deinhardt F., Schödel F. 1993; Principal neutralizing domain of HIV-1 is highly immunogenic when expressed on the surface of hepatitis B core particles. Vaccine 11:817–824
    [Google Scholar]
  24. Yoshikawa A., Tanaka T., Hoshi Y., Kato N., Tachibana K., Iizuka H., Machida A., Okamoto H., Yamasaki M., Miyakawa Y., Mayumi M. 1993; Chimeric hepatitis B virus core particles with parts or copies of the hepatitis C virus core protein. Journal of Virology 67:6064–6070
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-78-8-2049
Loading
/content/journal/jgv/10.1099/0022-1317-78-8-2049
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error