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
2020-10-21
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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 Medicine171:1815–1820
    [Google Scholar]
  2. Amengual B., Whitby J. E., Cobo J. S., Bourhy H.. 1997; Evolution of European bat lyssaviruses. Journal of General Virology78:2319–2328
    [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 Virology71:2292–2302
    [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. Vaccine16:417–425
    [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 Virology66:1199–1201
    [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 Virology65:4198–4203
    [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 Immunology157:3242–3249
    [Google Scholar]
  8. Bourhy H., Kissi B., Tordo N.. 1993; Molecular diversity of the Lyssavirus genus. Virology194:70–81
    [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 Virology64:6090–6100
    [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 Virology64:3804–3809
    [Google Scholar]
  11. Donnelly J. J., Ulmer J. B., Shiver J. W., Liu M. A.. 1997; DNA vaccines. Annual Review of Immunology15:617–648
    [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. Immunity7:97–112
    [Google Scholar]
  13. Commission European. 1996; COST/STD-3. Advantages of combined vaccines. Vaccine14:693–700
    [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. Vaccine6:533–539
    [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 Immunology7:797–805
    [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 Research54:165–187
    [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 Virology79:83–90
    [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 Virology73:225–233
    [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. Biologicals19:113–123
    [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. Lancet349:1663–1665
    [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 Medicine4:949–952
    [Google Scholar]
  22. Maniatis T., Fritsch E. F., Sambrook J.. 1982; Molecular Cloning. A Laboratory Manual Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  23. Martins L. P., Lau L. L., Asano M. S., Ahmed R.. 1995; DNA vaccination against persistent viral infection. Journal of Virology69:2574–2582
    [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 Virology51:107–114
    [Google Scholar]
  25. Pastoret P.-P., Brochier B., Aguilar-Setién A., Blancou J.. 1997; Vaccination against rabies. In Veterinary Vaccinology pp616–628 Edited by Pastoret P.-P., Blancou J., Vannier P., Verschuren C.. Amsterdam: Elsevier;
    [Google Scholar]
  26. Perrin P.. 1996; Techniques for the preparation of rabies conjugates. In Laboratory Techniques in Rabies pp433–445 Edited by Meslin F.-X., Kaplan M., Koprowski H.. Geneva: WHO;
    [Google Scholar]
  27. Perrin P., Thibodeau L., Sureau P.. 1985; Rabies immunosome (subunit vaccine) structure and immunogenicity. Pre- and post-exposure protection studies. Vaccine3:325–332
    [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 Standardization14:95–102
    [Google Scholar]
  29. Perrin P., Joffret M.-L., Leclerc C., Oth D., Sureau P., Thibodeau L.. 1988; Interleukin 2 increases protection against experimental rabies. Immunobiology177:199–209
    [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 Virology147:289–299
    [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 USA94:3314–3319
    [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 pp181–189 Edited by Meslin F.-X., Kaplan M., Koprowski H. Geneva: WHO;
    [Google Scholar]
  33. Spier R. E.. 1997; Multivalent vaccines: prospects and challenges. Folia Microbiologica42:105–112
    [Google Scholar]
  34. Suhrbier A.. 1997; Multi-epitope DNA vaccines. Immunological Cell Biology75:402–408
    [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 Immunology160:1717–1723
    [Google Scholar]
  36. Yokoyama M., Zhang J., Whitton J. L.. 1995; DNA immunization confers protection against lethal lymphocytic choriomeningitis virus infection. Journal of Virology69:2684–2688
    [Google Scholar]
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