1887

Journal of General Virology header logo

Volume 82, Issue 9

Construction and characterization of recombinant vaccinia viruses co-expressing a respiratory syncytial virus protein and a cytokine Free

Abstract

Recombinant vaccinia viruses are well-characterized tools that can be used to define novel approaches to vaccine formulation and delivery. While vector co-expression of immune mediators has enormous potential for optimizing the composition of vaccine-induced immune responses, the impact on antigen expression and vector antigenicity must also be considered. Co-expression of IL-4 increased vaccinia virus vector titres, while IFN-γ co-expression reduced vaccinia virus replication in BALB/c mice and in C57BL/6 mice infected with some recombinant viruses. Protection against respiratory syncytial virus (RSV) challenge was similar in mice immunized with vaccinia virus expressing RSV G glycoprotein and IFN-γ, even though the replication efficiency of the vector was diminished. These data demonstrate the ability of vector-expressed cytokine to influence the virulence of the vector and to direct the development of selected immune responses. This suggests that the co-expression of cytokines and other immunomodulators has the potential to improve the safety of vaccine vectors while improving the immunogenicity of vaccine antigens.

  • Received:
  • Accepted:
  • Published Online:
© Microbiology Society
Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-82-9-2107
2001-09-01
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/jgv/82/9/0822107a.html?itemId=/content/journal/jgv/10.1099/0022-1317-82-9-2107&mimeType=html&fmt=ahah

References

  1. Alcamí A., Smith G. L. 1995; Vaccinia, cowpox, and camelpox viruses encode soluble gamma interferon receptors with novel broad species specificity. Journal of Virology 69:4633–4639
     [Google Scholar]
  2. Alwan W. H., Openshaw P. J. M. 1993; Distinct patterns of T- and B-cell immunity to respiratory syncytial virus induced by individual viral proteins. Vaccine 11:431–437
     [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. Andrew M. E., Coupar B. E. H., Ada G. L., Boyle D. B. 1986; Cell-mediated immune responses to influenza virus antigens expressed by vaccinia virus recombinants. Microbial Pathogenesis 1:443–452
     [Google Scholar]
  5. Andrew M. E., Coupar B. E. H., Boyle D. B. 1989; Humoral and cell-mediated immune responses to recombinant vaccinia viruses in mice. Immunology and Cell Biology 67:331–337
     [Google Scholar]
  6. Aung S., Tang Y.-W., Graham B. S. 1999; Interleukin-4 diminishes CD8+ respiratory syncytial virus-specific cytotoxic T-lymphocyte activity in vivo. Journal of Virology 73:8944–8949
     [Google Scholar]
  7. Baumgarth N., Kelso A. 1996; In vivo blockade of gamma interferon affects the influenza virus-induced humoral and the local cellular immune response in lung tissue. Journal of Virology 70:4411–4418
     [Google Scholar]
  8. Bembridge G. P., Garcia-Beato R., Lopez J. A., Melero J. A., Taylor G. 1998a; Subcellular site of expression and route of vaccination influence pulmonary eosinophilia following respiratory syncytial virus challenge in BALB/c mice sensitized to the attachment G protein. Journal of Immunology 161:2473–2480
     [Google Scholar]
  9. Bembridge G. P., Lopez J. A., Cook R., Melero J. A., Taylor G. 1998b; Recombinant vaccinia virus coexpressing the F protein of respiratory syncytial virus (RSV) and interleukin-4 (IL-4) does not inhibit the development of RSV-specific memory cytotoxic T lymphocytes, whereas priming is diminished in the presence of high levels of IL-2 or gamma interferon. Journal of Virology 72:4080–4087
     [Google Scholar]
  10. Boyle D. B., Coupar B. E. H. 1986; Identification and cloning of the fowlpox virus thymidine kinase gene using vaccinia virus. Journal of General Virology 67:1591–1600
     [Google Scholar]
  11. Bukreyev A., Whitehead S. S., Bukreyeva N., Murphy B. R., Collins P. L. 1999; Interferon γ expressed by a recombinant respiratory syncytial virus attenuates virus replication in mice without compromising immunogenicity. Proceedings of the National Academy of Sciences, USA 96:2367–2372
     [Google Scholar]
  12. Chakrabarti S., Brechling K., Moss B. 1985; Vaccinia virus expression vector: coexpression of β-galactosidase provides visual screening of recombinant virus plaques. Molecular and Cellular Biology 5:3403–3409
     [Google Scholar]
  13. Coupar B. E. H., Boyle D. B., Both G. W. 1987; Effect of in vitro mutations in a vaccinia virus early promoter region monitored by herpes simplex virus thymidine kinase expression in recombinant vaccinia virus. Journal of General Virology 68:2299–2309
     [Google Scholar]
  14. Coupar B. E. H., Andrew M. E., Boyle D. B. 1988; A general method for the construction of recombinant vaccinia viruses expressing multiple foreign genes. Gene 68:1–10
     [Google Scholar]
  15. Davis N. L., Brown K. W., Johnston R. E. 1996; A viral vaccine vector that expresses foreign genes in lymph nodes and protects against mucosal challenge. Journal of Virology 70:3781–3787
     [Google Scholar]
  16. Doherty P. C., Allan W., Boyle D. B., Coupar B. E. H., Andrew M. E. 1989; Recombinant vaccinia viruses and the development of immunization strategies using influenza virus. Journal of Infectious Diseases 159:1119–1122
     [Google Scholar]
  17. Fischer J. E., Johnson J. E., Kuli-Zade R. K., Johnson T. R., Aung S., Parker R. A., Graham B. S. 1997; Overexpression of interleukin-4 delays virus clearance in mice infected with respiratory syncytial virus. Journal of Virology 71:8672–8677
     [Google Scholar]
  18. Flexner C., Moss B., London W. T., Murphy B. R. 1990; Attenuation and immunogenicity in primates of vaccinia virus recombinants expressing human interleukin-2. Vaccine 8:17–21
     [Google Scholar]
  19. Graham B. S. 1995; Pathogenesis of respiratory syncytial virus vaccine-augmented pathology. American Journal of Respiratory and Critical Care Medicine 152:S63–S66
     [Google Scholar]
  20. Graham B. S., Perkins M. D., Wright P. F., Karzon D. T. 1988; Primary respiratory syncytial virus infection in mice. Journal of Medical Virology 26:153–162
     [Google Scholar]
  21. Graham B. S., Bunton L. A., Wright P. F., Karzon D. T. 1991; Role of T lymphocyte subsets in the pathogenesis of primary infection and rechallenge with respiratory syncytial virus in mice. Journal of Clinical Investigation 88:1026–1033
     [Google Scholar]
  22. Hancock G. E., Speelman D. J., Heers K., Bortell E., Smith J., Cosco C. 1996; Generation of atypical pulmonary inflammatory responses in BALB/c mice after immunization with the native attachment (G) glycoprotein of respiratory syncytial virus. Journal of Virology 70:7783–7791
     [Google Scholar]
  23. Harris N., Buller R. M., Karupiah G. 1995; Gamma interferon-induced, nitric oxide-mediated inhibition of vaccinia virus replication. Journal of Virology 69:910–915
     [Google Scholar]
  24. Hsu K.-H. L., Lubeck M. D., Bhat B. M., Bhat R. A., Kostek B., Selling B. H., Mizutani S., Davis A. R., Hung P. P. 1994; Efficacy of adenovirus-vectored respiratory syncytial virus vaccines in a new ferret model. Vaccine 12:607–612
     [Google Scholar]
  25. Hu F. Q., Smith C. A., Pickup D. J. 1994; Cowpox virus contains two copies of an early gene encoding a soluble secreted form of the type II TNF receptor. Virology 204:343–356
     [Google Scholar]
  26. Hussell T., Openshaw P. J. M. 1998; Intracellular IFN-γ expression in natural killer cells precedes lung CD8+ T cell recruitment during respiratory syncytial virus infection. Journal of General Virology 79:2593–2601
     [Google Scholar]
  27. Hussell T., Baldwin C. J., O’Garra A., Openshaw P. J. M. 1997; CD8+ T cells control Th2-driven pathology during pulmonary respiratory syncytial virus infection. European Journal of Immunology 27:3341–3349
     [Google Scholar]
  28. Hussell T., Georgiou A., Sparer T. E., Matthews S., Pala P., Openshaw P. J. M. 1998; Host genetic determinants of vaccine-induced eosinophilia during respiratory syncytial virus infection. Journal of Immunology 161:6215–6222
     [Google Scholar]
  29. Johnson T. R., Graham B. S. 1999; Secreted respiratory syncytial virus G glycoprotein induces interleukin-5 (IL-5), IL-13, and eosinophilia by an IL-4-independent mechanism. Journal of Virology 73:8485–8495
     [Google Scholar]
  30. Johnson T. R., Johnson J. E., Roberts S. R., Wertz G. W., Parker R. A., Graham B. S. 1998; Priming with secreted glycoprotein G of respiratory syncytial virus (RSV) augments interleukin-5 production and tissue eosinophilia after RSV challenge. Journal of Virology 72:2871–2880
     [Google Scholar]
  31. Joklik W. K. 1985; Molecular biology of vaccinia virus: structure of poxvirus DNA. In Vaccinia Viruses as Vectors for Vaccine Antigens vol 1 pp 15–36 Edited by Quinnan G. V. Jr New York: Elsevier;
     [Google Scholar]
  32. Karupiah G., Woodhams C. E., Blanden R. V., Ramshaw I. A. 1991; Immunobiology of infection with recombinant vaccinia virus encoding murine-IL-2. Journal of Immunology 147:4327–4332
     [Google Scholar]
  33. Karupiah G., Xie Q. W., Buller R. M. L., Nathan C., Duarte C., MacMicking J. D. 1993; Inhibition of viral replication by interferon-γ-induced nitric oxide synthase. Science 261:1445–1448
     [Google Scholar]
  34. Kopf M., Le Gros G., Bachmann M., Lamers M. C., Bluethmann H., Kohler G. 1993; Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature 362:245–248
     [Google Scholar]
  35. Lee M. S., Roos J. M., McGuigan L. C., Smith K. A., Cormier N., Cohen L. K., Roberts B. E., Payne L. G. 1992; Molecular attenuation of vaccinia virus: mutant generation and animal characterization. Journal of Virology 66:2617–2630
     [Google Scholar]
  36. Levine S., Dillman T. R., Montgomery P. C. 1989; The envelope proteins from purified respiratory syncytial virus protect mice from intranasal virus challenge. Proceedings of the Society for Experimental Biology and Medicine 190:349–356
     [Google Scholar]
  37. Lucey D. R., Clerici M., Shearer G. M. 1996; Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases. Clinical Microbiology Reviews 9:532–562
     [Google Scholar]
  38. Mackett M., Smith G. L., Moss B. 1982; Vaccinia virus: a selectable eukaryotic cloning and expression vector. Proceedings of the National Academy of Sciences, USA 79:7415–7419
     [Google Scholar]
  39. Mars M., Beaud G. 1987; Characterization of vaccinia virus early promoters and evaluation of their informational content. Journal of Molecular Biology 198:619–631
     [Google Scholar]
  40. Mathews J. H., Kinney R. M., Roehrig J. T., Barrett A. D. T., Trent D. W. 1994; Murine T-helper cell immune response to recombinant vaccinia–Venezuelan equine encephalitis virus. Vaccine 12:620–624
     [Google Scholar]
  41. Murphy B. R., Sotnikov A., Paradiso P. R., Hildreth S. W., Jenson A. B., Baggs R. B., Lawrence L., Zubak J. J., Chanock R. M., Beeler J. A., Prince G. A. 1989; Immunization of cotton rats with the fusion (F) and large (G) glycoproteins of respiratory syncytial virus (RSV) protects against RSV challenge without potentiating RSV disease. Vaccine 7:533–540
     [Google Scholar]
  42. Olmsted R. A., Elango N., Prince G. A., Murphy B. R., Johnson P. R., Moss B., Chanock R. M., Collins P. L. 1986; Expression of the F glycoprotein of respiratory syncytial virus by a recombinant vaccinia virus: comparison of the individual contributions of the F and G glycoproteins to host immunity. Proceedings of the National Academy of Sciences, USA 83:7462–7466
     [Google Scholar]
  43. Olmsted R. A., Buller R. M., Collins P. L., London W. T., Beeler J. A., Prince G. A., Chanock R. M., Murphy B. R. 1988; Evaluation in non-human primates of the safety, immunogenicity and efficacy of recombinant vaccinia viruses expressing the F or G glycoprotein of respiratory syncytial virus. Vaccine 6:519–524
     [Google Scholar]
  44. Openshaw P. J. M., Clarke S. L., Record F. M. 1992; Pulmonary eosinophilic response to respiratory syncytial virus infection in mice sensitized to the major surface glycoprotein G. International Immunology 4:493–500
     [Google Scholar]
  45. Palumbo G. J., Buller R. M., Glasgow W. C. 1994; Multigenic evasion of inflammation by poxviruses. Journal of Virology 68:1737–1749
     [Google Scholar]
  46. Perkus M. E., Tartaglia J., Paoletti E. 1995; Poxvirus-based vaccine candidates for cancer, AIDS, and other infectious diseases. Journal of Leukocyte Biology 58:1–13
     [Google Scholar]
  47. Piedra P. A., Faden H. S., Camussi G., Wong D. T., Ogra P. L. 1989; Mechanism of lung injury in cotton rats immunized with formalin-inactivated respiratory syncytial virus. Vaccine 7:34–38
     [Google Scholar]
  48. Ramshaw I. A., Andrew M. E., Phillips S. M., Boyle D. B., Coupar B. E. H. 1987; Recovery of immunodeficient mice from a vaccinia virus/IL-2 recombinant infection. Nature 329:545–546
     [Google Scholar]
  49. Roberts S. R., Lichtenstein D. L., Ball L. A., Wertz G. W. 1994; The membrane-associated and secreted forms of the respiratory syncytial virus attachment glycoprotein G are synthesized from alternative initiation codons. Journal of Virology 68:4538–4546
     [Google Scholar]
  50. Ruby J., Ramshaw I. A. 1991; The antiviral activity of immune CD8+ T cells is dependent on interferon-γ. Lymphokine and Cytokine Research 10:353–358
     [Google Scholar]
  51. Sharma D. P., Ramsay A. J., Maguire D. J., Rolph M. S., Ramshaw I. A. 1996; Interleukin-4 mediates down regulation of antiviral cytokine expression and cytotoxic T-lymphocyte responses and exacerbates vaccinia virus infection in vivo. Journal of Virology 70:7103–7107
     [Google Scholar]
  52. Sparer T. E., Matthews S., Hussell T., Rae A. J., Garcia-Barreno B., Melero J. A., Openshaw P. J. M. 1998; Eliminating a region of respiratory syncytial virus attachment protein allows induction of protective immunity without vaccine-enhanced lung eosinophilia. Journal of Experimental Medicine 187:1921–1926
     [Google Scholar]
  53. Srikiatkhachorn A., Braciale T. J. 1997a; Virus-specific memory and effector T lymphocytes exhibit different cytokine responses to antigens during experimental murine respiratory syncytial virus infection. Journal of Virology 71:678–685
     [Google Scholar]
  54. Srikiatkhachorn A., Braciale T. J. 1997b; Virus-specific CD8+ T lymphocytes downregulate T helper cell type 2 cytokine secretion and pulmonary eosinophilia during experimental murine respiratory syncytial virus infection. Journal of Experimental Medicine 186:421–432
     [Google Scholar]
  55. Srikiatkhachorn A., Chang W., Braciale T. J. 1999; Induction of Th-1 and Th-2 responses by respiratory syncytial virus attachment glycoprotein is epitope and major histocompatibility complex independent. Journal of Virology 73:6590–6597
     [Google Scholar]
  56. Takao S.-I., Kiyotani K., Sakaguchi T., Fujii Y., Seno M., Yoshida T. 1997; Protection of mice from respiratory Sendai virus infections by recombinant vaccinia viruses. Journal of Virology 71:832–838
     [Google Scholar]
  57. Tang Y.-W., Graham B. S. 1996; Potential for directing appropriate responses to vaccines by cytokine manipulation. Clinical Immunotherapeutics 5:327–333
     [Google Scholar]
  58. Tang Y.-W., Graham B. S. 1997; T cell source of type 1 cytokines determines illness patterns in respiratory syncytial virus-infected mice. Journal of Clinical Investigation 99:2183–2191
     [Google Scholar]
  59. Tebbey P. W., Hagen M., Hancock G. E. 1998; Atypical pulmonary eosinophilia is mediated by a specific amino acid sequence of the attachment (G) protein of respiratory syncytial virus. Journal of Experimental Medicine 188:1967–1972
     [Google Scholar]
  60. Varga S. M., Wissinger E. L., Braciale T. J. 2000; The attachment (G) glycoprotein of respiratory syncytial virus contains a single immunodominant epitope that elicits both Th1 and Th2 CD4+ T cell responses. Journal of Immunology 165:6487–6495
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-82-9-2107
Loading
Construction and characterization of recombinant vaccinia viruses co-expressing a respiratory syncytial virus protein and a cytokine
J. Gen. Virol. 82, 2107 (2001); https://doi.org/10.1099/0022-1317-82-9-2107
/content/journal/jgv/10.1099/0022-1317-82-9-2107
/content/journal/jgv/10.1099/0022-1317-82-9-2107
Loading

Data & Media loading...

Most cited Most Cited RSS feed

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