1887

Abstract

Truncated and chimeric lyssavirus glycoprotein (G) genes were used to carry and express non-lyssavirus B and T cell epitopes for DNA-based immunization of mice, with the aim of developing a multivalent vaccine prototype. Truncated G (GPVIII) was composed of the C-terminal half (aa 253–503) of the Pasteur rabies virus (PV: genotype 1) G containing antigenic site III and the transmembrane and cytoplasmic domains. The chimeric G (GEBL1-PV) was composed of the N-terminal half (aa 1–250) of the European bat lyssavirus 1 (genotype 5) G containing antigenic site II linked to GPVIII. Antigenic sites II and III are involved in the induction of virus-neutralizing antibodies. The B cell epitope was the C3 neutralization epitope of the poliovirus type 1 capsid VP1 protein. The T cell epitope was the H2 MHC I-restricted epitope of the nucleoprotein of lymphocytic choriomeningitis virus (LCMV) involved in the induction of both cytotoxic T cell (CTL) production and protection against LCMV. Truncated G carrying foreign epitopes induced weak antibody production against rabies and polio viruses and provided weak protection against LCMV. In contrast, the chimeric plasmid containing various combinations of B and CTL epitopes elicited simultaneous immunological responses against both parental lyssaviruses and poliovirus and provided good protection against LCMV. The level of humoral and cellular immune responses depended on the order of the foreign epitopes inserted. Our results demonstrate that chimeric lyssavirus glycoproteins can be used not only to broaden the spectrum of protection against lyssaviruses, but also to express foreign B and CTL epitopes. The potential usefulness of chimeric lyssavirus glycoproteins for the development of multivalent vaccines against animal diseases and zoonoses, including rabies, is discussed.

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1999-09-01
2020-01-20
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References

  1. Aichele, P., Hengartner, H., Zinkernagel, R. M. & Schulz, M. ( 1990; ). Antiviral cytotoxic T cell response induced by in vivo priming with a free synthetic peptide. Journal of Experimental Medicine 171, 1815-1820.[CrossRef]
    [Google Scholar]
  2. Amengual, B., Whitby, J. E., Cobo, J. S. & Bourhy, H. ( 1997; ). Evolution of European bat lyssaviruses. Journal of General Virology 78, 2319-2328.
    [Google Scholar]
  3. An, L.-L. & Whitton, J. L. ( 1997; ). A multivalent minigene vaccine, containing B-cell, cytotoxic T-lymphocyte, and Th epitopes from several microbes, induces appropriate responses in vivo and confers protection against more than one pathogen. Journal of Virology 71, 2292-2302.
    [Google Scholar]
  4. Bahloul, C., Jacob, Y., Tordo, N. & Perrin, P. ( 1998; ). DNA-based immunization for exploring the enlargement of immunological cross-reactivity against the lyssaviruses. Vaccine 16, 417-425.[CrossRef]
    [Google Scholar]
  5. Battegay, M., Oehen, S., Schulz, M., Hengartner, H. & Zinkernagel, R. M. ( 1992; ). Vaccination with a synthetic peptide modulates lymphocytic choriomeningitis virus-mediated immunopathology. Journal of Virology 66, 1199-1201.
    [Google Scholar]
  6. Benmansour, A., Leblois, H., Coulon, P., Tuffereau, C., Gaudin, Y., Flamand, A. & Lafay, F. ( 1991; ). Antigenicity of rabies virus glycoprotein. Journal of Virology 65, 4198-4203.
    [Google Scholar]
  7. Bergmann, C. C., Yao, Q., Ho, C.-K. & Buckwold, S. L. ( 1996; ). Flanking residues alter antigenicity and immunogenicity of multi-unit CTL epitopes. Journal of Immunology 157, 3242-3249.
    [Google Scholar]
  8. Bourhy, H., Kissi, B. & Tordo, N. ( 1993; ). Molecular diversity of the Lyssavirus genus. Virology 194, 70-81.[CrossRef]
    [Google Scholar]
  9. Delpeyroux, F., Van Wezel, E., Blondel, B. & Crainic, R. ( 1990; ). Structural factors modulate the activity of antigenic poliovirus sequences expressed on hybrid hepatitis B surface antigen particles. Journal of Virology 64, 6090-6100.
    [Google Scholar]
  10. Dietzschold, B., Gore, M., Marchadier, D., Niu, H.-S., Bunschoten, H. M., Otvos, L.Jr, Wunner, W. H., Ertl, H. C., Osterhaus, A. D. & Koprowski, H. ( 1990; ). Structural and immunological characterization of a linear virus-neutralizing epitope of the rabies virus glycoprotein and its possible use in a synthetic vaccine. Journal of Virology 64, 3804-3809.
    [Google Scholar]
  11. Donnelly, J. J., Ulmer, J. B., Shiver, J. W. & Liu, M. A. ( 1997; ). DNA vaccines. Annual Review of Immunology 15, 617-648.[CrossRef]
    [Google Scholar]
  12. Doolan, D. L., Hoffman, S. L., Southwood, S., Wentworth, P. A., Sidney, J., Chesnut, R. W., Keogh, E., Appella, E., Nutman, T. B., Lal, A. A., Gordon, D. M., Oloo, A. & Sette, A. ( 1997; ). Degenerate cytotoxic T cell epitopes from P. falciparum restricted by multiple HLA-A and HLA-B supertype alleles. Immunity 7, 97-112.[CrossRef]
    [Google Scholar]
  13. European Commission ( 1996; ). COST/STD-3. Advantages of combined vaccines. Vaccine 14, 693–700.
    [Google Scholar]
  14. Fekadu, M., Shaddock, J. H., Sanderlin, D. W. & Smith, J. S. ( 1988; ). Efficacy of rabies vaccines against Duvenhage virus isolated from European house bats (Eptesicus serotinus), classic rabies and rabies-related viruses. Vaccine 6, 533-539.[CrossRef]
    [Google Scholar]
  15. Goossens, P. L., Milon, G., Cossart, P. & Saron, M.-F. ( 1995; ). Attenuated Listeria monocytogenes as a live vector for induction of CD8+ T cells in vivo: a study with the nucleoprotein of the lymphocytic choriomeningitis virus. International Immunology 7, 797-805.[CrossRef]
    [Google Scholar]
  16. Gould, A. R., Hyatt, A. D., Lunt, R., Kattenbelt, J. A., Hengstberger, S. & Blacksell, S. D. ( 1998; ). Characterisation of a novel lyssavirus isolated from Pteropid bats in Australia. Virus Research 54, 165-187.[CrossRef]
    [Google Scholar]
  17. Hanke, T., Blanchard, T. J., Schneider, J., Ogg, G. S., Tan, R., Becker, M., Gilbert, S. C., Hill, A. V. S., Smith, G. L. & McMichael, A. ( 1998; ). Immunogenicities of intravenous and intramuscular administrations of modified vaccinia virus Ankara-based multi-CTL epitope vaccine for human immunodeficiency virus type 1 in mice. Journal of General Virology 79, 83-90.
    [Google Scholar]
  18. Jallet, C., Jacob, Y., Bahloul, C., Drings, A., Desmézières, E., Tordo, N. & Perrin, P. ( 1999; ). Chimeric lyssavirus glycoproteins with increased immunological potential. Journal of Virology 73, 225-233.
    [Google Scholar]
  19. Joffret, M.-L., Zanetti, C., Morgeaux, S., Leclerc, C., Sureau, P. & Perrin, P. ( 1991; ). Appraisal of rabies vaccine potency by determination of in vitro, specific interleukin-2 production. Biologicals 19, 113-123.[CrossRef]
    [Google Scholar]
  20. Lang, J., Duong, G. H., Nguyen, V. G., Le, T. T., Nguyen, C. V., Kesmedjian, V. & Plotkin, S. A. ( 1997; ). Randomised feasibility trial of pre-exposure rabies vaccination with DTP-IPV in infants. Lancet 349, 1663-1665.[CrossRef]
    [Google Scholar]
  21. Lodmell, D. L., Ray, N. B., Parnell, M. J., Ewalt, L. C., Hanlon, C. A., Shaddock, J. H., Sanderlin, D. S. & Rupprecht, C. E. ( 1998; ). DNA immunization protects non-human primates against rabies virus. Nature Medicine 4, 949-952.[CrossRef]
    [Google Scholar]
  22. Maniatis, T., Fritsch, E. F. & Sambrook, J. (1982). Molecular Cloning. A Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  23. Martins, L. P., Lau, L. L., Asano, M. S. & Ahmed, R. ( 1995; ). DNA vaccination against persistent viral infection. Journal of Virology 69, 2574-2582.
    [Google Scholar]
  24. Park, J. Y., Peters, C. J., Rollin, P. E., Ksiazek, T. G., Gray, B., Waites, K. B. & Stephensen, C. B. ( 1997; ). Development of a reverse transcription-polymerase chain reaction assay for diagnosis of lymphocytic choriomeningitis virus infection and its use in a prospective surveillance study. Journal of Medical Virology 51, 107-114.[CrossRef]
    [Google Scholar]
  25. Pastoret, P.-P., Brochier, B., Aguilar-Setién, A. & Blancou, J. ( 1997; ). Vaccination against rabies. In Veterinary Vaccinology, pp. 616-628. Edited by P.-P. Pastoret, J. Blancou, P. Vannier & C. Verschuren. Amsterdam: Elsevier.
  26. Perrin, P. ( 1996; ). Techniques for the preparation of rabies conjugates. In Laboratory Techniques in Rabies, pp. 433-445. Edited by F.-X. Meslin, M. Kaplan & H. Koprowski. Geneva: WHO.
  27. Perrin, P., Thibodeau, L. & Sureau, P. ( 1985; ). Rabies immunosome (subunit vaccine) structure and immunogenicity. Pre- and post-exposure protection studies. Vaccine 3, 325-332.[CrossRef]
    [Google Scholar]
  28. Perrin, P., Versmisse, P., Delagneau, J. F., Lucas, G., Rollin, P. E. & Sureau, P. ( 1986; ). The influence of the type of immunosorbent on rabies antibody EIA; advantages of purified glycoprotein over whole virus. Journal of Biological Standardization 14, 95-102.[CrossRef]
    [Google Scholar]
  29. Perrin, P., Joffret, M.-L., Leclerc, C., Oth, D., Sureau, P. & Thibodeau, L. ( 1988; ). Interleukin 2 increases protection against experimental rabies. Immunobiology 177, 199-209.
    [Google Scholar]
  30. Perrin, P., De Franco, M., Jallet, C., Fouque, F., Morgeaux, S., Tordo, N. & Colle, J.-H. ( 1996; ). The antigen-specific cell-mediated immune response in mice is suppressed by infection with pathogenic lyssaviruses. Research in Virology 147, 289-299.[CrossRef]
    [Google Scholar]
  31. Saron, M.-F., Fayolle, C., Sebo, P., Ladant, D., Ullmann, A. & Leclerc, C. ( 1997; ). Anti-viral protection conferred by recombinant adenylate cyclase toxins from Bordetella pertussis carrying a CD8+ T cell epitope from lymphocytic choriomeningitis virus. Proceedings of the National Academy of Sciences, USA 94, 3314-3319.[CrossRef]
    [Google Scholar]
  32. Smith, J., Yager, P. & Baer, G. ( 1996; ). A rapid fluorescent focus inhibition test (RFFIT) for determining virus-neutralizing antibody. In Laboratory Techniques in Rabies, pp. 181-189. Edited by F.-X. Meslin, M. Kaplan & H. Koprowski. Geneva: WHO.
  33. Spier, R. E. ( 1997; ). Multivalent vaccines: prospects and challenges. Folia Microbiologica 42, 105-112.[CrossRef]
    [Google Scholar]
  34. Suhrbier, A. ( 1997; ). Multi-epitope DNA vaccines. Immunological Cell Biology 75, 402-408.[CrossRef]
    [Google Scholar]
  35. Thomson, S. A., Sherritt, M. A., Medveczky, J., Elliott, S. L., Moss, D. J., Fernando, G. J., Brown, L. E. & Suhrbier, A. ( 1998; ). Delivery of multiple CD8 cytotoxic T cell epitopes by DNA vaccination. Journal of Immunology 160, 1717-1723.
    [Google Scholar]
  36. Yokoyama, M., Zhang, J. & Whitton, J. L. ( 1995; ). DNA immunization confers protection against lethal lymphocytic choriomeningitis virus infection. Journal of Virology 69, 2684-2688.
    [Google Scholar]
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