1887

Journal of General Virology header logo

Volume 73, Issue 2

Construction of vaccinia virus recombinants expressing several measles virus proteins and analysis of their efficacy in vaccination of mice Free

Abstract

Measles virus genes encoding the haemagglutinin (HA), fusion protein (F) or nucleoprotein (NP) have been inserted into the vaccinia virus genome either alone or in various combinations. In each case the measles virus genes were expressed from the 7.5K promoter and were incorporated into the thymidine kinase (tk) or K1L loci of the Copenhagen strain of vaccinia virus. Cells infected by the recombinants synthesized measles virus proteins indistinguishable from those induced in measles virus-infected cells. However, in some instances the level of expression in cells infected by recombinants expressing more than one measles virus gene was reduced when compared to those encoding a single gene. The sera from mice immunized with recombinants containing either HA, HA.F, HA.NP or HA.F.NP had similar levels of measles virus neutralizing antibodies which remained constant throughout a 7 month period. Analysis of these sera by immunoprecipitation of radiolabelled measles virus confirmed the presence of specific antibody to each of the antigens where appropriate. The introduction of the measles virus genes into the K1L and the tk sites despite attenuating the virus for mice by 10-fold and 1000-fold respectively did not affect the vaccination efficiency, i.e. ability to induce measles virus antibody and protect mice. Vaccination of BALB/c (H2d) mice with HA and F, but not NP, recombinants completely protected the animals against a lethal measles virus challenge. In contrast, although the HA recombinant protected CBA (H2k) mice, the F recombinant did so poorly. However, by immunizing CBA mice with a recombinant expressing both F and NP, protection was increased to more than 75%. Our findings demonstrate the ability of three measles virus antigens expressed from the vaccinia virus genome alone or in combination to contribute to protective immunity against measles virus infection of mice. They also suggest that the association of measles virus antigens in a single recombinant DNA vaccine could be beneficial to overcome host-related restriction of the immune response to particular antigens.

  • Received:
  • Accepted:
  • Published Online:
© Journal of General Virology 1992
Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-73-2-359
1992-02-01
2024-04-16
Loading full text...

Full text loading...

/deliver/fulltext/jgv/73/2/JV0730020359.html?itemId=/content/journal/jgv/10.1099/0022-1317-73-2-359&mimeType=html&fmt=ahah

References

  1. Bangham C. R. M., Openshaw P. J. M., Ball L. A., King A. M. Q., Wertz G. W., Askonas B. A. 1986; Human and murine cytotoxic T cells specific to respiratory syncytial virus recognize the viral nucleoprotein (N), but not the major glycoprotein (G) expressed by vaccinia virus recombinants. Journal of Immunology 137:3973–3977
     [Google Scholar]
  2. Bankamp B., Brinckmann U. G., Reich A., Niewiesk S., ter Meulen V., Liebert U. 1991; Measles virus nucleocapsid protein protects rats from encephalitis. Journal of Virology 65:1695–1700
     [Google Scholar]
  3. Bennink J. R., Yewdell J. W. 1990; Recombinant vaccinia viruses as vectors for studying T lymphocyte specificity and function. In Poxviruses, Current Topics in Microbiology and Immunology pp 153–184 Edited by Moyer R. W., Turner P. C. Berlin: Springer Verlag;
     [Google Scholar]
  4. Buckland R., Gerald C., Barker R., Wild T. F. 1987; Fusion glycoprotein of measles virus: nucleotide sequence of the gene and comparison with other paramyxoviruses. Journal of General Virology 68:1695–1703
     [Google Scholar]
  5. Buckland R., Gerald C., Barker R., Wild T. F. 1988; Cloning and sequencing of the nucleoprotein gene of measles virus (Hallé strain). Nucleic Acids Research 16:11821
     [Google Scholar]
  6. Buller R. M. L., Smith G. L., Cremer K., Notkins A. L., Moss B. 1985; Decreased virulence of recombinant vaccinia virus expression vectors is associated with a thymidine kinase-negative phenotype. Nature, London 317:813–815
     [Google Scholar]
  7. Chakrabarti S., Brechling K., Moss B. 1985; Vaccinia virus expression vector: coexpression of β-galactosidase provides visual screening of recombinant plaques. Molecular and Cellular Biology 5:3403–3409
     [Google Scholar]
  8. Drillien R., Spehner D., Kirn A. 1982; Complementation and genetic linkage between vaccinia virus temperature-sensitive mutants. Virology 119:372–381
     [Google Scholar]
  9. Drillien R., Spehner D., Kirn A., Giraudon P., Buckland R., Wild T. F., Lecocq J. -P. 1988; Protection of mice from fatal measles encephalitis by vaccination with vaccinia virus recombinants encoding either the hemagglutinin or the fusion protein. Proceedings of the National Academy of Sciences, U.S.A. 85:1252–1256
     [Google Scholar]
  10. Enders J. F., McCarthy K., Mitus A., Cheatham W. J. 1959; Isolation of measles virus at autopsy in cases of giant cell pneumonia without rash. New England Journal of Medicine 261:875–881
     [Google Scholar]
  11. Ertl H. C. J., Dietzschold B., Gore M., Otuosjr L., Larson J. K., Wunner W. H., Koprowski H. 1989; Induction of rabies virus-specific T-helper cells by synthetic peptides that carry dominant T-helper cell epitopes of the viral ribonucleoprotein. Journal of Virology 63:2885–2892
     [Google Scholar]
  12. Fulginiti V. A., Eller J. J., Downie A. W., Kempe C. H. 1967; Altered reactivity to measles virus. Atypical measles in children previously immunized with inactivated measles virus vaccines. Journal of the American Medical Association 202:1075–1080
     [Google Scholar]
  13. Fulginiti V. A., Eller J. J., Sieber O. F., Joyner J. W., Minamitani M., Meiklejohn G. 1969; Respiratory virus immunization 1. A field trial of two inactivated 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]
  14. Gao J. L.-M., Liew F. Y., Tite J. P. 1989; Identification and characterization of T helper epitopes in the nucleoprotein of influenza A virus. Journal of Immunology 143:3007–3014
     [Google Scholar]
  15. Gerald C., Buckland R., Barker R., Freeman G., Wild T. F. 1986; Measles virus haemagglutinin gene: cloning, complete sequence analysis and expression in COS cells. Journal of General Virology 67:2695–2703
     [Google Scholar]
  16. Gillard S., Spehner D., Drillien R. 1985; Mapping of a vaccinia host range sequence by insertion into the thymidine kinase gene. Journal of Virology 53:316–318
     [Google Scholar]
  17. Gillard S., Spehner D., Drillien R., Kirn A. 1986; Localization and sequence of a vaccinia virus gene required for multiplication in human cells. Proceedings of the National Academy of Sciences, U.S.A 83:5573–5577
     [Google Scholar]
  18. Goebel S. J., Johnson G. P., Perkus M. E., Davis S. W., Winslow J. P., Paoletti E. 1990; The complete DNA sequence of vaccinia virus. Virology 179:247–266
     [Google Scholar]
  19. Good R. A., Zak S. J. 1956; Disturbances in gamma globulin synthesis as “experiments of nature”. Pediatrics 18:109–149
     [Google Scholar]
  20. Hall C. V., Jacob P. E., Ringold G. M., Lee F. 1983; Expression and regulation of Escherichia coli lacZ gene fusions in mammalian cells. Journal of Molecular and Applied Genetics 2:101–109
     [Google Scholar]
  21. Hruby D. E., Maki R. A., Miller D. B., Ball L. A. 1983; Fine structure analysis and nucleotide sequence of the vaccinia virus thymidine gene. Proceedings of the National Academy of Science, U.S.A 80:3411–3415
     [Google Scholar]
  22. Kieny M. P., Lathe R., Drillien R., Spehner D., Skory S., Schmitt D., Wiktor T., Koprowski H., Lecocq J. P. 1984; Expression of rabies virus glycoprotein from a recombinant vaccinia virus. Nature, London 312:163–166
     [Google Scholar]
  23. Kim H. W., Canchola J. G., Brandt C. D., Pyles G., Chanock R. M., Jensen K., Parrot 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]
  24. Lathe R., Vilotte J. C., Clarke A. J. 1987; Plasmid and bacteriophage vectors for expression of intact inserts. Gene 57:193–201
     [Google Scholar]
  25. Mackett M., Smith G. L., Moss B. 1982; Vaccinia virus: a selectable eukaryotic cloning and expression vector. Proceedings of the National Academy of Sciences, U.S.A. 79:7415–7419
     [Google Scholar]
  26. McMichael A. J., Michie C. A., Gotch F. M., Smith G. L., Moss B. 1986; Recognition of influenza A nucleoprotein by human cytotoxic T lymphocytes. Journal of General Virology 67:719–726
     [Google Scholar]
  27. Mal voisin E., Wild F. 1990; Contribution of measles virus fusion protein in protective immunity: anti-F monoclonal antibodies neutralize virus infectivity and protect mice against challenge. Journal of Virology 64:5160–5162
     [Google Scholar]
  28. Mason P. W., Pincus S., Fournier M. J., Mason T. L., Shope R. E., Paoletti E. 1991; Japanese encephalitis virus-vaccinia recombinants produce particulate forms of the structural membrane proteins and induce high levels of protection against lethal JEV infection. Virology 180:294–305
     [Google Scholar]
  29. Mitus A., Enders J. F., Edsall G., Holloway A. 1985; Measles in children with malignancy: problems and prevention. Archiv fur die Gesamte Virusforschung 16:331–337
     [Google Scholar]
  30. Norrby E., Enders-Ruckle G., ter Meulen V. 1975; Differences in the appearance of antibodies to structural components of measles virus after immunization with inactivated and live virus. Journal of Infectious Diseases 132:262–269
     [Google Scholar]
  31. 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]
  32. Panicali D., Grzelecki A., Huang C. 1986; Vaccinia virus vectors utilizing the β-galactosidase assay for rapid selection of recombinant viruses and measurement of gene expression. Gene 47:193–199
     [Google Scholar]
  33. 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]
  34. Perkus M. E., Piccini A., Lipinskas B. R., Paoletti E. 1985; Recombinant vaccinia virus: immunization against multiple pathogens. Science 229:981–984
     [Google Scholar]
  35. Perkus M. E., Limbach K., Paoletti E. 1989; Cloning and expression of foreign genes in vaccinia virus using a host range selection system. Journal of Virology 63:3829–3836
     [Google Scholar]
  36. Perkus M. E., Goebel S. J., Davis S. W., Johnson G. P., Limbach K., Norton E. K., Paoletti E. 1990; Vaccinia virus host range genes. Virology 179:276–286
     [Google Scholar]
  37. Perkus M. E., Goebel S. J., Davis S. W., Johnson G. P., Norton E. K., Paoletti E. 1991; Deletion of 55 open reading frames from the termini of vaccinia virus. Virology 180:406–410
     [Google Scholar]
  38. Piccini A., Paoletti E. 1988; Vaccinia: virus, vector, vaccine. Advances in Virus Research 34:43–64
     [Google Scholar]
  39. Puddington L., Bevan M. J., Rose J. K., Lefrancois L. 1986; N protein is the predominant antigen recognized by vesicular stomatitis virus-specific cytotoxic cells. Journal of Virology 60:708–717
     [Google Scholar]
  40. Sato T. A., Kohama T., Sugiura A. 1989; Protective role of human antibody to the fusion protein of measles virus. Microbiology and Immunology 33:601–607
     [Google Scholar]
  41. Spehner D., Drillien R., Lecocq J. P. 1990; Construction of fowlpox virus vectors with intergenic insertions: expression of the β-galactosidase gene and the measles virus fusion gene. Journal of Virology 64:527–533
     [Google Scholar]
  42. Ttte J. P., Russell S. M., Dougan G., O’Callaghan D., Jones I., Brownlee G., Liew F. Y. 1988; Antiviral immunity induced by recombinant nucleoprotein of influenza A virus. I. Characterization and cross-reactivity of T cell responses. Journal of Immunology 141:3980–3987
     [Google Scholar]
  43. Townsend A. R. M., McMichael A. J., Carter N. P., Huddles-ton J. A., Brownlee G. G. 1984; Cytotoxic T cell recognition of the influenza nucleoprotein and hemagglutinin expressed in transfected mouse L cells. Cell 39:13–25
     [Google Scholar]
  44. Van Binnendijk R. S., Poelen M. C., Kuijpers K. C., Osterhaus A. D. M. E., UytdeHaag G. C. M. 1990; The predominance of CD8+ T cells after infection with measles virus suggests a role for CD8+ class I MHC restricted cytotoxic T lymphocytes (CTL) in recovery from measles: clonal analyses of human CD8+ class I MHC restricted CTL. Journal of Immunology 144:2394–2399
     [Google Scholar]
  45. Weir J. P., Moss B. 1983; Nucleotide sequence of the vaccinia virus thymidine kinase gene and the nature of spontaneous frameshift mutants. Journal of Virology 46:530–537
     [Google Scholar]
  46. Wild T. F., Giraudon P., Bernard A., Huppert J. 1979; Isolation and characterization of a defective measles virus from a subacute sclerosing panencephalitis patient. Journal of Medical Virology 4:103–114
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-73-2-359
Loading
Construction of vaccinia virus recombinants expressing several measles virus proteins and analysis of their efficacy in vaccination of mice
J. Gen. Virol. 73, 359 (1992); https://doi.org/10.1099/0022-1317-73-2-359
/content/journal/jgv/10.1099/0022-1317-73-2-359
/content/journal/jgv/10.1099/0022-1317-73-2-359
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