1887

Abstract

Chimeric (D2/WN) viruses containing the pre-membrane (prM) and envelope (E) proteins of (WN virus) and the capsid (C) and non-structural proteins of dengue 2 (DEN2) virus were used to evaluate the protective immunity elicited by either the flaviviral E protein or non-structural proteins. AG129 interferon-deficient mice, previously shown to be protected against lethal DEN1 or DEN2 viral infection after vaccination with a wild-type or candidate vaccine strain of DEN1 or DEN2 virus, respectively, were immunized with chimeric D2/WN virus and then challenged with DEN2 virus. D2/WN chimeric viruses were non-pathogenic in AG129 mice. These viruses elicited little anti-DEN E antibody, high levels of anti-DEN NS1 antibody and no or very low levels of DEN2 virus-neutralizing antibodies. Only 15 % of D2/WN-immunized mice survived challenge with DEN2 virus. However, their mean survival time increased by 11–14 days over non-immunized controls. These results suggest that, whilst the non-structural proteins were able to enhance mean survival times of AG129 mice, this protection was not as effective as protection mediated by the E protein.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81256-0
2006-02-01
2019-11-14
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/2/339.html?itemId=/content/journal/jgv/10.1099/vir.0.81256-0&mimeType=html&fmt=ahah

References

  1. Arroyo, J., Guirakhoo, F., Fenner, S., Zhang, Z.-X., Monath, T. P. & Chambers, T. J. ( 2001; ). Molecular basis for attenuation of neurovirulence of a yellow fever virus/Japanese encephalitis virus chimera vaccine (ChimeriVax-JE). J Virol 75, 934–942.[CrossRef]
    [Google Scholar]
  2. Blitvich, B. J., Marlenee, N. L., Hall, R. A., Calisher, C. H., Bowen, R. A., Roehrig, J. T., Komar, N., Langevin, S. A. & Beaty, B. J. ( 2003; ). Epitope-blocking enzyme-linked immunosorbent assays for the detection of serum antibodies to West Nile virus in multiple avian species. J Clin Microbiol 41, 1041–1047.[CrossRef]
    [Google Scholar]
  3. Bray, M., Zhao, B., Markoff, L., Eckels, K. H., Chanock, R. M. & Lai, C.-J. ( 1989; ). Mice immunized with recombinant vaccinia virus expressing dengue 4 virus structural proteins with or without nonstructural protein NS1 are protected against fatal dengue virus encephalitis. J Virol 63, 2853–2856.
    [Google Scholar]
  4. Bray, M., Men, R. & Lai, C.-J. ( 1996; ). Monkeys immunized with intertypic chimeric dengue viruses are protected against wild-type virus challenge. J Virol 70, 4162–4166.
    [Google Scholar]
  5. Caufour, P. S., Motta, M. C. A., Yamamura, A. M. Y., Vazquez, S., Ferreira, I. I., Jabor, A. V., Bonaldo, M. C., Freire, M. S. & Galler, R. ( 2001; ). Construction, characterization and immunogenicity of recombinant yellow fever 17D-dengue type 2 viruses. Virus Res 79, 1–14.[CrossRef]
    [Google Scholar]
  6. Chambers, T. J., Liang, Y., Droll, D. A., Schlesinger, J. J., Davidson, A. D., Wright, P. J. & Jiang, X. ( 2003; ). Yellow fever virus/dengue-2 virus and yellow fever virus/dengue-4 virus chimeras: biological characterization, immunogenicity, and protection against dengue encephalitis in the mouse model. J Virol 77, 3655–3668.[CrossRef]
    [Google Scholar]
  7. Falgout, B., Bray, M., Schlesinger, J. J. & Lai, C.-J. ( 1990; ). Immunization of mice with recombinant vaccinia virus expressing authentic dengue virus nonstructural protein NS1 protects against lethal dengue virus encephalitis. J Virol 64, 4356–4363.
    [Google Scholar]
  8. Gubler, D. J. ( 1998; ). Dengue and dengue hemorrhagic fever. Clin Microbiol Rev 11, 480–496.
    [Google Scholar]
  9. Guirakhoo, F., Weltzin, R., Chambers, T. J. & 7 other authors ( 2000; ). Recombinant chimeric yellow fever-dengue type 2 virus is immunogenic and protective in nonhuman primates. J Virol 74, 5477–5485.[CrossRef]
    [Google Scholar]
  10. Hall, R. A., Brand, T. N. H., Lobigs, M., Sangster, M. Y., Howard, M. J. & Mackenzie, J. S. ( 1996; ). Protective immune responses to the E and NS1 proteins of Murray Valley encephalitis virus in hybrids of flavivirus-resistant mice. J Gen Virol 77, 1287–1294.[CrossRef]
    [Google Scholar]
  11. Halstead, S. B. & O'Rourke, E. J. ( 1977; ). Dengue virus and mononuclear phagocytes. I. Infection enhancement by non-neutralizing antibody. J Exp Med 146, 201–217.[CrossRef]
    [Google Scholar]
  12. Huang, C. Y.-H., Butrapet, S., Pierro, D. J., Chang, G.-J. J., Hunt, A. R., Bhamarapravati, N., Gubler, D. J. & Kinney, R. M. ( 2000; ). Chimeric dengue type 2 (vaccine strain PDK-53)/dengue type 1 virus as a potential candidate dengue type 1 virus vaccine. J Virol 74, 3020–3028.[CrossRef]
    [Google Scholar]
  13. Huang, C. Y.-H., Butrapet, S., Tsuchyia, K. R., Bhamarapravati, N., Gubler, D. J. & Kinney, R. M. ( 2003; ). Dengue 2 PDK-53 virus as a chimeric carrier for tetravalent dengue vaccine development. J Virol 77, 11436–11447.[CrossRef]
    [Google Scholar]
  14. Huang, C. Y.-H., Silengo, S. J., Whiteman, M. C. & Kinney, R. M. ( 2005; ). Chimeric dengue 2 PDK-53/West Nile NY99 viruses retain the phenotypic attenuation markers of the candidate PDK-53 vaccine virus and protect mice against lethal challenge with West Nile virus. J Virol 79, 7300–7310.[CrossRef]
    [Google Scholar]
  15. Jacobs, S. C., Stephenson, J. R. & Wilkinson, G. W. G. ( 1992; ). High-level expression of the tick-borne encephalitis virus NS1 protein by using an adenovirus-based vector: protection elicited in a murine model. J Virol 66, 2086–2095.
    [Google Scholar]
  16. Jacobs, S. C., Stephenson, J. R. & Wilkinson, G. W. G. ( 1994; ). Protection elicited by a replication-defective adenovirus vector expressing the tick-borne encephalitis virus non-structural glycoprotein NS1. J Gen Virol 75, 2399–2402.[CrossRef]
    [Google Scholar]
  17. Johnson, A. J. & Roehrig, J. T. ( 1999; ). New mouse model for dengue virus vaccine testing. J Virol 73, 783–786.
    [Google Scholar]
  18. Konishi, E., Pincus, S., Fonseca, B. A. L., Shope, R. E., Paoletti, E. & Mason, P. W. ( 1991; ). Comparison of protective immunity elicited by recombinant vaccinia viruses that synthesize E or NS1 of Japanese encephalitis virus. Virology 185, 401–410.[CrossRef]
    [Google Scholar]
  19. Kurane, I., Innis, B. L., Nimmannitya, S., Nisalak, A., Meager, A., Janus, J. & Ennis, F. A. ( 1991; ). Activation of T lymphocytes in dengue virus infections: high levels of soluble interleukin 2 receptor, soluble CD4, soluble CD8, interleukin 2, and interferon-γ in sera of children with dengue. J Clin Invest 88, 1473–1480.[CrossRef]
    [Google Scholar]
  20. Lin, Y.-L., Chen, L.-K., Liao, C.-L., Yeh, C.-T., Ma, S.-H., Chen, J.-L., Huang, Y.-L., Chen, S.-S. & Chiang, H.-Y. ( 1998; ). DNA immunization with Japanese encephalitis virus nonstructural protein NS1 elicits protective immunity in mice. J Virol 72, 191–200.
    [Google Scholar]
  21. Littaua, R., Kurane, I. & Ennis, F. A. ( 1990; ). Human IgG Fc receptor II mediates antibody-dependent enhancement of dengue virus infection. J Immunol 144, 3183–3186.
    [Google Scholar]
  22. Lobigs, M., Arthur, C. E., Müllbacher, A. & Blanden, R. V. ( 1994; ). The flavivirus nonstructural protein NS3 is a dominant source of cytotoxic T cell peptide determinants. Virology 202, 195–201.[CrossRef]
    [Google Scholar]
  23. Monath, T. P. ( 1994; ). Dengue: the risk to developed and developing countries. Proc Natl Acad Sci U S A 91, 2395–2400.[CrossRef]
    [Google Scholar]
  24. Muller, U., Steinhoff, U., Reis, L. F., Hemmi, S., Pavlovic, J., Zinkernagel, R. M. & Aguet, M. ( 1994; ). Functional role of type I and type II interferons in antiviral defense. Science 264, 1918–1921.[CrossRef]
    [Google Scholar]
  25. Obijeski, J. F., Bishop, D. H. L., Murphy, F. A. & Palmer, E. L. ( 1976; ). Structural proteins of La Crosse virus. J Virol 19, 985–997.
    [Google Scholar]
  26. Pletnev, A. G., Bray, M., Hanley, K. A., Speicher, J. & Elkins, R. ( 2001; ). Tick-borne langat/mosquito-borne dengue flavivirus chimera, a candidate live attenuated vaccine for protection against disease caused by members of the tick-borne encephalitis virus complex: evaluation in rhesus monkeys and in mosquitoes. J Virol 75, 8259–8267.[CrossRef]
    [Google Scholar]
  27. Pletnev, A. G., Claire, M. S., Elkins, R., Speicher, J., Murphy, B. R. & Chanock, R. M. ( 2003; ). Molecularly engineered live-attenuated chimeric West Nile/dengue virus vaccines protect rhesus monkeys from West Nile virus. Virology 314, 190–195.[CrossRef]
    [Google Scholar]
  28. Pugachev, K. V., Mason, P. W., Shope, R. E. & Frey, T. K. ( 1995; ). Double-subgenomic Sindbis virus recombinants expressing immunogenic proteins of Japanese encephalitis virus induce significant protection in mice against lethal JEV infection. Virology 212, 587–594.[CrossRef]
    [Google Scholar]
  29. Qu, X., Chen, W., Maguire, T. & Austin, F. ( 1993; ). Immunoreactivity and protective effects in mice of a recombinant dengue 2 Tonga virus NS1 protein produced in a baculovirus expression system. J Gen Virol 74, 89–97.[CrossRef]
    [Google Scholar]
  30. Reed, L. J. & Muench, H. ( 1938; ). A simple method of estimating fifty percent endpoints. Am J Hyg 27, 493–497.
    [Google Scholar]
  31. Roehrig, J. T. ( 2003; ). Antigenic structure of flavivirus protein. Adv Virus Res 59, 141–175.
    [Google Scholar]
  32. Schlesinger, J. J., Foltzer, M. & Chapman, S. ( 1993; ). The Fc portion of antibody to yellow fever virus NS1 is a determinant of protection against YF encephalitis in mice. Virology 192, 132–141.[CrossRef]
    [Google Scholar]
  33. Shresta, S., Kyle, J. L., Snider, H. M., Basavapatna, M., Beatty, P. R. & Harris, E. ( 2004; ). Interferon-dependent immunity is essential for resistance to primary dengue virus infection in mice, whereas T- and B-cell-dependent immunity are less critical. J Virol 78, 2701–2710.[CrossRef]
    [Google Scholar]
  34. Spaulding, A., Kurane, I., Ennis, F. A. & Rothman, A. L. ( 1999; ). Analysis of murine CD8+ T-cell clones specific for the dengue virus NS3 protein: flavivirus cross-reactivity and influence of infecting serotype. J Virol 73, 398–403.
    [Google Scholar]
  35. van den Broek, M. F., Muller, U., Huang, S., Aguet, M. & Zinkernagel, R. M. ( 1995; ). Antiviral defense in mice lacking both alpha/beta and gamma interferon receptors. J Virol 69, 4792–4796.
    [Google Scholar]
  36. van der Most, R. G., Murali-Krishna, K., Ahmed, R. & Strauss, J. H. ( 2000; ). Chimeric yellow fever/dengue virus as a candidate dengue vaccine: quantitation of the dengue virus-specific CD8 T-cell response. J Virol 74, 8094–8101.[CrossRef]
    [Google Scholar]
  37. Zhang, Y.-M., Hayes, E. P., McCarty, T. C., Dubois, D. R., Summers, P. L., Eckels, K. H., Chanock, R. M. & Lai, C.-J. ( 1988; ). Immunization of mice with dengue structural proteins and nonstructural protein NS1 expressed by baculovirus recombinant induces resistance to dengue virus encephalitis. J Virol 62, 3027–3031.
    [Google Scholar]
  38. Zhao, B. T., Prince, G., Horswood, R., Eckels, K., Summers, P., Chanock, R. & Lai, C.-J. ( 1987; ). Expression of dengue virus structural proteins and nonstructural protein NS1 by a recombinant vaccinia virus. J Virol 61, 4019–4022.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81256-0
Loading
/content/journal/jgv/10.1099/vir.0.81256-0
Loading

Data & Media loading...

Most Cited This Month

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