1887

Abstract

The capacity of DNA vaccines to prime CD8+ T cells makes them excellent candidates for vaccines that are designed to emphasize cellular immunity. However, the long-term stability of CD8+ T cell memory induced by DNA vaccination is poorly characterized. Here, the quality of CD8+ T cell recall responses in mice was investigated more than 1 year after DNA vaccination with the Sendai virus nucleoprotein gene. Cytotoxic T lymphocyte (CTL) activity specific for both dominant and subdominant epitopes could be recalled readily 1 year after vaccination and the frequencies of CTL precursors specific for both of these epitopes were relatively high. These CTL responded strongly to subsequent Sendai virus infection in terms of their ability to migrate to the lung and to differentiate into effector cells. In addition, the recall response to virus infection, as determined by CTL activity in the lungs and IFN-gamma responses in the spleen, was both faster and greater in magnitude than that in control-immunized mice. Significantly, virus titres were reduced at least 100-fold in the lungs of mice that were immunized more than 1 year before infection, as compared with control mice. These data demonstrate that CD8+ T cell memory elicited by DNA vaccination is functionally relevant and persists for at least 1 year.

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1999-06-01
2024-04-19
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References

  1. Ahmed R., Gray D. 1996; Immunological memory and protective immunity: understanding their relation. Science 272:54–60
    [Google Scholar]
  2. Allan W., Tabi Z., Cleary A., Doherty P. C. 1990; Cellular events in the lymph node and lung of mice with influenza. Consequences of depleting CD4 + T cells. Journal of Immunology 144:3980–3986
    [Google Scholar]
  3. Asano M. S., Ahmed R. 1996; CD8 T cell memory in B cell-deficient mice. Journal of Experimental Medicine 183:2165–2174
    [Google Scholar]
  4. Boyer J. D., Ugen K. E., Wang B., Agadjanyan M., Gilbert L., Bagarazzi M. L., Chattergoon M., Frost P., Javadian A., Williams W. V., Refaeli Y., Ciccarelli R. B., McCallus D., Coney L., Weiner D. B. 1997; Protection of chimpanzees from high-dose heterologous HIV-1 challenge by DNA vaccination. Nature Medicine 3:526–532
    [Google Scholar]
  5. Calarota S., Bratt G., Nordlund S., Hinkula J., Leandersson A. C., Sandstrom E., Wahren B. 1998; Cellular cytotoxic response induced by DNA vaccination in HIV-1-infected patients. Lancet 351:1320–1325
    [Google Scholar]
  6. Cardoso A. I., Blixenkrone-Moller M., Fayolle J., Liu M., Buckland R., Wild T. F. 1996; Immunization with plasmid DNA encoding for the measles virus hemagglutinin and nucleoprotein leads to humoral and cell-mediated immunity. Virology 225:293–299
    [Google Scholar]
  7. Chen Y., Webster R. G., Woodland D. L. 1998; Induction of CD8+ T cell responses to dominant and subdominant epitopes and protective immunity to Sendai virus infection by DNA vaccination. Journal of Immunology 160:2425–2432
    [Google Scholar]
  8. Cole G. A., Katz J. M., Hogg T. L., Ryan K. W., Portner A., Woodland D. L. 1994; Analysis of the primary T-cell response to Sendai virus infection in C57BL/6 mice: CD4+ T-cell recognition is directed predominantly to the hemagglutinin–neuraminidase glycoprotein. Journal of Virology 68:6863–6870
    [Google Scholar]
  9. Cole G. A., Hogg T. L., Coppola M. A., Woodland D. L. 1997; Efficient priming of CD8+ memory T cells specific for a subdominant epitope following Sendai virus infection. Journal of Immunology 158:4301–4309
    [Google Scholar]
  10. Condon C., Watkins S. C., Celluzzi C. M., Thompson K., Falo L. D. Jr 1996; DNA-based immunization by in vivo transfection of dendritic cells. Nature Medicine 2:1122–1128
    [Google Scholar]
  11. Davis H. L., Schirmbeck R., Reimann J., Whalen R. G. 1995; DNA-mediated immunization in mice induces a potent MHC class I-restricted cytotoxic T lymphocyte response to the hepatitis B envelope protein. Human Gene Therapy 6:1447–1456
    [Google Scholar]
  12. Davis H. L., Millan C. L., Watkins S. C. 1997; Immune-mediated destruction of transfected muscle fibers after direct gene transfer with antigen-expressing plasmid DNA. Gene Therapy 4:181–188
    [Google Scholar]
  13. Di Rosa F., Matzinger P. 1996; Long-lasting CD8 T cell memory in the absence of CD4 T cells or B cells. Journal of Experimental Medicine 183:2153–2163
    [Google Scholar]
  14. Flynn K. J., Belz G. T., Altman J. D., Ahmed R., Woodland D. L., Doherty P. C. 1998; Virus-specific CD8+ T cells in primary and secondary influenza pneumonia. Immunity 8:683–691
    [Google Scholar]
  15. Fu T. M., Friedman A., Ulmer J. B., Liu M. A., Donnelly J. J. 1997; Protective cellular immunity: cytotoxic T-lymphocyte responses against dominant and recessive epitopes of influenza virus nucleoprotein induced by DNA immunization. Journal of Virology 71:2715–2721
    [Google Scholar]
  16. Gonzalez Armas J. C., Morello C. S., Cranmer L. D., Spector D. H. 1996; DNA immunization confers protection against murine cyto-megalovirus infection. Journal of Virology 70:7921–7928
    [Google Scholar]
  17. Gray D., Matzinger P. 1991; T cell memory is short-lived in the absence of antigen. Journal of Experimental Medicine 174:969–974
    [Google Scholar]
  18. Hou S., Doherty P. C., Zijlstra M., Jaenisch R., Katz J. M. 1992; Delayed clearance of Sendai virus in mice lacking class I MHC-restricted CD8+ T cells. Journal of Immunology 149:1319–1325
    [Google Scholar]
  19. Hou S., Fishman M., Murti K. G., Doherty P. C. 1993; Divergence between cytotoxic effector function and tumor necrosis factor alpha production for inflammatory CD4 + T cells from mice with Sendai virus pneumonia. Journal of Virology 67:6299–6302
    [Google Scholar]
  20. Hou S., Hyland L., Ryan K. W., Portner A., Doherty P. C. 1994; Virus-specific CD8 + T-cell memory determined by clonal burst size. Nature 369:652–654
    [Google Scholar]
  21. Kappler J. W., Skidmore B., White J., Marrack P. 1981; Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition. Journal of Experimental Medicine 153:1198–1214
    [Google Scholar]
  22. Kast W. M., Roux L., Curren J., Blom H. J., Voordouw A. C., Meloen R. H., Kolakofsky D., Melief C. J. 1991; Protection against lethal Sendai virus infection by in vivo priming of virus-specific cytotoxic T lymphocytes with a free synthetic peptide. Proceedings of the National Academy of Sciences, USA 88:2283–2287
    [Google Scholar]
  23. Klinman D. M., Sechler J. M., Conover J., Gu M., Rosenberg A. S. 1998; Contribution of cells at the site of DNA vaccination to the generation of antigen-specific immunity and memory. Journal of Immunology 160:2388–2392
    [Google Scholar]
  24. Lagging L. M., Meyer K., Hoft D., Houghton M., Belshe R. B., Ray R. 1995; Immune responses to plasmid DNA encoding the hepatitis C virus core protein. Journal of Virology 69:5859–5863
    [Google Scholar]
  25. Lau L. L., Jamieson B. D., Somasundaram T., Ahmed R. 1994; Cytotoxic T-cell memory without antigen. Nature 369:648–652
    [Google Scholar]
  26. Lu S., Arthos J., Montefiori D. C., Yasutomi Y., Manson K., Mustafa F., Johnson E., Santoro J. C., Wissink J., Mullins J. I., Haynes J. R., Letvin N. L., Wyand M., Robinson H. L. 1996; Simian immunodeficiency virus DNA vaccine trial in macaques. Journal of Virology 70:3978–3991
    [Google Scholar]
  27. MacGregor R. R., Boyer J. D., Ugen K. E., Lacy K. E., Gluckman S. J., Bagarazzi M. L., Chattergoon M. A., Baine Y., Higgins T. J., Ciccarelli R. B., Coney L. R., Ginsberg R. S., Weiner D. B. 1998; First human trial of a DNA-based vaccine for treatment of human immunodeficiency virus type 1 infection: safety and host response. Journal of Infectious Diseases 178:92–100
    [Google Scholar]
  28. Manning W. C., Paliard X., Zhou S., Pat Bland M., Lee A. Y., Hong K., Walker C. M., Escobedo J. A., Dwarki V. 1997; Genetic immunization with adeno-associated virus vectors expressing herpes simplex virus type 2 glycoproteins B and D. Journal of Virology 71:7960–7962
    [Google Scholar]
  29. Ostrand-Rosenberg S., Roby C., Clements V. K., Cole G. A. 1991; Tumor-specific immunity can be enhanced by transfection of tumor cells with syngeneic MHC-class-II genes or allogeneic MHC-class-I genes. International Journal of Cancer Suppl 6:61–68
    [Google Scholar]
  30. Pertmer T. M., Eisenbraun M. D., McCabe D., Prayaga S. K., Fuller D. H., Haynes J. R. 1995; Gene gun-based nucleic acid immunization: elicitation of humoral and cytotoxic T lymphocyte responses following epidermal delivery of nanogram quantities of DNA. Vaccine 13:1427–1430
    [Google Scholar]
  31. Raz E., Carson D. A., Parker S. E., Parr T. B., Abai A. M., Aichinger G., Gromkowski S. H., Singh M., Lew D., Yankauckas M. A. and others 1994; Intradermal gene immunization: the possible role of DNA uptake in the induction of cellular immunity to viruses. Proceedings of the National Academy of Sciences, USA 91:9519–9523
    [Google Scholar]
  32. Torres C. A., Iwasaki A., Barber B. H., Robinson H. L. 1997; Differential dependence on target site tissue for gene gun and intramuscular DNA immunizations. Journal of Immunology 158:4529–4532
    [Google Scholar]
  33. Townsend A. R., Rothbard J., Gotch F. M., Bahadur G., Wraith D., McMichael A. J. 1986; The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell 44:959–968
    [Google Scholar]
  34. Ulmer J. B., Donnelly J. J., Parker S. E., Rhodes G. H., Felgner P. L., Dwarki V. J., Gromkowski S. H., Deck R. R., DeWitt C. M., Friedman A. and others 1993; Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259:1745–1749
    [Google Scholar]
  35. Whitmore A. C., Gooding L. R. 1981; Specificities of killing by T lymphocytes generated against syngeneic SV40 transformants: crossreactivity of the H-2Kbm1 through Kbm4 H-2 mutant alleles in Kb-restricted SV40-specific killing. Journal of Immunology 127:1207–1211
    [Google Scholar]
  36. Wolff J. A., Ludtke J. J., Acsadi G., Williams P., Jani A. 1992; Long-term persistence of plasmid DNA and foreign gene expression in mouse muscle. Human Molecular Genetics 1:363–369
    [Google Scholar]
  37. Yankauckas M. A., Morrow J. E., Parker S. E., Abai A., Rhodes G. H., Dwarki V. J., Gromkowski S. H. 1993; Long-termanti-nucleoprotein cellular and humoral immunity is induced by intramuscular injection of plasmid DNA containing NP gene. DNA Cell Biology 12:771–776
    [Google Scholar]
  38. Yasutomi Y., Robinson H. L., Lu S., Mustafa F., Lekutis C., Arthos J., Mullins J. I., Voss G., Manson K., Wyand M., Letvin N. L. 1996; Simian immunodeficiency virus-specific cytotoxic T-lymphocyte induction through DNA vaccination of rhesus monkeys. Journal of Virology 70:678–681
    [Google Scholar]
  39. Yokoyama M., Zhang J., Whitton J. L. 1995; DNA immunization confers protection against lethal lymphocytic choriomeningitis virus infection. Journal of Virology 69:2684–2688
    [Google Scholar]
  40. Zarozinski C. C., Fynan E. F., Selin L. K., Robinson H. L., Welsh R.M. 1995; Protective CTL-dependent immunity and enhanced immunopathology in mice immunized by particle bombardment with DNA encoding an internal virion protein. Journal of Immunology 154:4010–4017
    [Google Scholar]
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