1887

Abstract

Vaccinia virus (vv) recombinants expressing either wild-type (VA-F) or mutant forms (VA-FT, VA-FR47, VA-FS1 to VA-FS6) of the fusion (F) protein of respiratory syncytial (RS) virus were examined for their ability to elicit antibody, cytotoxic T lymphocytes (CTL) and protection against RS virus infection in BALB/c mice. Cells infected with the VA-F and VA-FT recombinants expressed the F protein on their surface and mice vaccinated with these recombinants developed RS virus neutralizing antibodies. The VA-FR47 recombinant expressed a mutant form of the F protein (with six amino acid changes from the wild-type) in which both proteolytic processing of the F precursor and its transport to the cell surface were inhibited. These mutants induced transient protection against RS virus infection although they did not induce RS virus neutralizing antibodies, or antibodies detectable by ELISA. All the vv recombinants were able to induce an RS virus-specific, MHC class I restricted CTL response. Vaccination of mice with a second set of vv recombinants expressing mutant forms of the F protein showed that the replacement Phe to Ser at amino acid 237 either alone or in combination with others abolished the neutralizing antibody response but did not affect priming of CTLs. These results demonstrate that long-term protection against RS virus infection in mice vaccinated with recombinant vv expressing the F protein is more dependent upon the induction of an antibody rather than a CTL response.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-77-6-1239
1996-06-01
2024-04-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/77/6/JV0770061239.html?itemId=/content/journal/jgv/10.1099/0022-1317-77-6-1239&mimeType=html&fmt=ahah

References

  1. 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]
  2. Alwan W. H., Record F. M., Openshaw P. J. M. 1992; CD4+ T cells clear virus but augment disease in mice infected with respiratory syncytial virus. Comparison with the effects of CD8+ T cells. Clinical and Experimental Immunology 88:527–536
    [Google Scholar]
  3. Alwan W. H., Kozlowska W. J., Openshaw P. J. M. 1994; Distinct types of lung disease caused by functional subsets of antiviral T cells. Journal of Experimental Medicine 179:81–89
    [Google Scholar]
  4. Bennink J. R., Yewdell J. W. 1990; Recombinant vaccinia viruses as vectors for studying T lymphocyte specificity and function. Current Topics in Microbiology and Immunology 163:155–183
    [Google Scholar]
  5. Cannon M. J., Stott E. J., Taylor G., Askonas B. A. 1987; Clearance of persistent respiratory syncytial virus infections in immunodeficient mice following transfer of primed T cells. Immunology 62:133–138
    [Google Scholar]
  6. Cannon M. J., Openshaw P. J. M., Askonas B. A. 1988; Cytotoxic T cells clear virus but augment lung pathology in mice infected with respiratory syncytial virus. Journal of Experimental Medicine 168:1163–1168
    [Google Scholar]
  7. Cherrie A. H., Anderson K., Wertz G. W., Openshaw P. J. M. 1992; Human cytotoxic T cells stimulated by antigen on dendritic cells recognise the N, SH, F, M, 22K and 1b proteins of respiratory syncytial virus. Journal of Virology 66:2102–2110
    [Google Scholar]
  8. Connors M., Collins P. L., Firestone C.-Y., Murphy B. R. 1991; Respiratory syncytial virus (RSV) F, G, M2 (22K) and N proteins each induce resistance to RSV challenge, but resistance induced by M2 and N proteins is relatively short-lived. Journal of Virology 65:1634–1637
    [Google Scholar]
  9. Connors M., Kulkarni A. B., Collins P. L., Firestone C.-Y., Holmes K. L., Morse H. C. III, Murphy B. R. 1992a; Resistance to respiratory syncytial virus (RSV) challenge induced by infection with a vaccinia virus recombinant expressing the RSV M2 protein (Vac-M2) is mediated by CD8+ T cells while that induced by Vac-F or Vac-G recombinants is mediated by antibodies. Journal of Virology 66:1277–1281
    [Google Scholar]
  10. Connors M., Kulkarni A. B., Firestone C. -Y., Holmes K. L., Morse H. C., Sotnikov A. V., Murphy B. R. 1992b; Pulmonary histopathology induced by respiratory syncytial virus (RSV) challenge of formalin-inactivated RSV-immunized BALB/c mice is abrogated by depletion of CD4+ T cells. Journal of Virology 66:7444–7451
    [Google Scholar]
  11. Connors M., Giese N. A., Kulkarni A. B., Firestone C. Y., Morse H. C. III, Murphy B. R. 1994; Enhanced pulmonary histopathology induced by respiratory syncytial virus (RSV) challenge of formalin-inactivated RSV-immunized BALB/c mice is abrogated by depletion of interleukin-4 (IL-4) and IL-10. Journal of Virology 68:5321–5325
    [Google Scholar]
  12. Del Val M., Schlicht H. L., Volkwer H., Messerle M., Reddehase M. J., Koszinowski W. H. 1991; Protection againt lethal cytomegalovirus infection by a recombinant vaccine containing a single nonameric T-cell epitope. Journal of General Virology 65:3641–3646
    [Google Scholar]
  13. Denny F. W., Taylor-Robinson D., Allison A. C. 1972; The role of the thymus-dependent immunity in Mycoplasma pulmonis infections of mice. Journal of Medical Microbiology 5:327–335
    [Google Scholar]
  14. Fernie B. F., Ford E. C., Gerin J. L. 1981; The development of BALB/c cells persistently infected with respiratory syncytial virus: presence of ribonucleoprotein on the cell surface. Proceedings of the Society for Experimental Biology and Medicine 167:83–86
    [Google Scholar]
  15. Fulginiti V. A., Eller J. J., Sieber O. F., Joyner J. W., Minamitani M., Meiklejohn G. 1969; Respiratory virus vaccines; an aqueous trivalent parainfluenza virus vaccine and an alum precipitated respiratory syncytial virus vaccine. American Journal of Epidemiology 89:435–448
    [Google Scholar]
  16. Garcia-Barreno B., Jorcano J. L., Aukenbauer C., Lopez-Galindez C., Melero J. A. 1988; Participation of cytoskeletal intermediate filaments in the infectious cycle of human respiratory syncytial virus (RSV). Virus Research 9:307–322
    [Google Scholar]
  17. Garcia-Barreno B., Palomo C., Penas C., Delgado T., Perez-Brena P., Melero J. A. 1989; Marked differences in the antigenic structure of human respiratory syncytial virus F and G glycoproteins. Journal of Virology 63:925–932
    [Google Scholar]
  18. Hall C. B., Douglas R. G. Jr, Geiman J. M. 1976; Respiratory syncytial virus infections in infants: quantitation and duration of shedding. Journal of Pediatrics 89:11–15
    [Google Scholar]
  19. Hany M., Oehen S., Schulz M., Hengartner H., Mackett M., Bishop D. H. L., Overton H., Zinkernagel R. M. 1989; Antiviral protection and prevention of lymphocytic choriomeningitis or of the local footpad swelling reaction in mice by immunization with vaccinia recombinant virus expressing LCMV-WE nucleoprotein or glycoprotein. European Journal of Immunology 19:417–424
    [Google Scholar]
  20. Kim H. W., Canchola J. G., Brandt C. D., Pyles G., Chanock R. M., Jensen K., Parrott R. H. 1969; Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. American Journal of Epidemiology 89:422–434
    [Google Scholar]
  21. Kimman T. G., Westenbrink F. 1990; Immunity to human and bovine respiratory syncytial virus. Archives of Virology 112:1–25
    [Google Scholar]
  22. Lawson C. M., Bennink J. R., Restifio N. P., Yewdell J. W., Murphy B. R. 1994; Primary pulmonary cytotoxic T lymphocytes induced by immunization with a vaccinia virus recombinant expressing influenza A virus nucleoprotein peptide do not protect mice against challenge. Journal of Virology 68:3505–3511
    [Google Scholar]
  23. Lopez J. A., Bustos R., Portela A., Garcia-Barreno B., Melero J. A. 1996; A point mutation in the F1 subunit of human respiratory syncytial virus F glycoprotein blocks its cell surface transport at an early stage of the exocytic pathway. Journal of General Virology 77:649–660
    [Google Scholar]
  24. McIntosh K., Chanock R. M. 1990; Respiratory syncytial virus. In Virology pp. 1045–1072 Edited by Fields B. N., Knipe D. M. New York: Raven Press;
    [Google Scholar]
  25. Nicholas J., Rubino K., Levely M., Adams E., Collins P. 1990; Cytolytic T-lymphocyte responses to respiratory syncytial virus: effector cell phenotype and target proteins. Journal of Virology 64:4232–4241
    [Google Scholar]
  26. Olmsted R. A., Elango N., Prince G. A. 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]
  27. Openshaw P. J. M., Pemberton R. M., Ball L. A., Wertz G. W., Askonas B. A. 1988; Helper T cell recognition of respiratory syncytial virus in mice. Journal of General Virology 69:305–312
    [Google Scholar]
  28. Openshaw P. J. M., Anderson K., Wertz G. W., Askonas B. A. 1990; The 22, 000–kilodalton protein of respiratory syncytial virus is a major target for Kd-restricted cytotoxic T lymphocytes from mice primed by infection. Journal of Virology 64:1683–1689
    [Google Scholar]
  29. Openshaw P. J. M., Clarke S. L., Record F. M. 1992; Pulmonary eosinophilic response to respiratory syncytial virus infection in mice sensitised to the major surface glycoprotein G. International Immunology 4:493–500
    [Google Scholar]
  30. Pemberton R. M., Cannon M. J., Openshaw P. J. M., Ball L. A., Wertz G. W., Askonas B. A. 1987; Cytotoxic T cell specificity for respiratory syncytial virus proteins: fusion protein is an important target antigen. Journal of General Virology 68:2177–2182
    [Google Scholar]
  31. Prince G. A., Jenson A. B., Hemming V. G., Murphy B. R., Walsh E. E., Horswood R. L., Chanock R. M. 1986; Enhancement of respiratory syncytial virus pulmonary pathology in cotton rats by prior intramuscular inoculation of formalin-inactivated virus. Journal of Virology 57:721–728
    [Google Scholar]
  32. Pringle C. 1987; Paramyxoviruses and diseases. In Molecular Basis of Virus Diseases pp. 51–90 Edited by Russell W. C., Almond J. W. Cambridge: Cambridge University Press;
    [Google Scholar]
  33. Rammensee H. G., Friede T., Stevanovic S. 1995; MHC ligands and peptide motifs: first listing. Immunogenetics 41:178–228
    [Google Scholar]
  34. Stott E. J., Taylor G. 1985; Respiratory syncytial virus. Archives of Virology 84:1–52
    [Google Scholar]
  35. Stott E. J., Taylor G., Ball L. A., Anderson K., Young K. K. Y., King A. M. Q., Wertz G. W. 1987; Immune and histopathological responses in animals vaccinated with recombinant vaccinia viruses that express individual genes of human respiratory syncytial virus. Journal of Virology 61:3855–3861
    [Google Scholar]
  36. Taylor G. 1994; The role of antibody in controlling and clearing virus infections. In Strategies in Vaccine Design pp. 17–34 Edited by Ada G. L. Austin: R. G. Landes;
    [Google Scholar]
  37. Taylor G., Stott E. J., Bew M., Fernie B. F., Cote P. J., Collins A. P., Hughes M., Jebbett J. 1984; Monoclonal antibodies protect against respiratory syncytial virus infection in mice. Immunology 52:137–142
    [Google Scholar]
  38. Taylor G., Stott E. J., Hayle A. J. 1985; Cytotoxic lymphocytes in the lungs of mice infected with respiratory syncytial virus. Journal of General Virology 66:2533–2538
    [Google Scholar]
  39. Taylor G., Stott E. J., Furze J., Ford J., Sopp P. 1992; Protective epitopes on the fusion protein of respiratory syncytial virus recognized by murine and bovine monoclonal antibodies. Journal of General Virology 73:2217–2223
    [Google Scholar]
  40. Tempest P. R., Bremner P., Lambert M., Taylor G., Furze J. M., Carr F. J., Harris W. J. 1991; Reshaping a human monoclonal antibody to inhibit human respiratory syncytial virus infection in vivo . Bio /Technology 9:266–271
    [Google Scholar]
  41. Towbin H., Staehelin T., Gordon J. 1979; Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proceedings of the National Academy of Sciences, USA 76:4350–4354
    [Google Scholar]
  42. Vaux-Peretz F., Meignier B. 1990; Comparison of lung histology and bronchoalveolar lavage cytology in mice and cotton rats infected with respiratory syncytial virus. Vaccine 8:543–547
    [Google Scholar]
  43. Walsh E. E., Schlesinger J. J., Brandriss M. W. 1984; Protection from respiratory syncytial virus infection in cotton rats by passive transfer of monoclonal antibodies. Infection and Immunity 43:756–758
    [Google Scholar]
  44. Zinkernagel R. M. 1976; H-2 compatibility requirement for virus-specific T cell-mediated effector functions in vivo.. Journal of Immunology 117:1495–1502
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-77-6-1239
Loading
/content/journal/jgv/10.1099/0022-1317-77-6-1239
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