Abstract
Nucleic acid immunization is a novel vaccination technique to induce antigen-specific immune responses. We have developed expression cassettes for cell surface markers CD80 and CD86, two functionally related costimulatory molecules that play an important role in the induction of T cell-mediated immune responses. Coimmunization of these expression plasmids, along with plasmid DNA encoding for HIV-1 antigens, did not result in any significant change in the humoral response; however, we observed a dramatic increase in cytotoxic T-lymphocyte (CTL) induction as well as T-helper cell proliferation after the coadministration of CD86 genes, in contrast, coimmunization with a CD80 expression cassette resulted in a minor, but positive increase in T-helper cell or CTL responses. This strategy may be of value for the generation of rationally designed vaccines and immune therapeutics.
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References
Kim, J.J., Ayyvoo, V., Bagarazzi, M.L., Chattergoon, M.A., Dang, K., Wang, B. et al. 1997 In vivo engineering of a cellular immune response by coadministration of IL-12 expression vector with a DMA immunogen. J. Immunol. 158: 816–826.
Boyer, J.D., Wang, B., Ugen, K., Agadjanyan, M.G., Javadian, MA, Frost, R. et al. 1996 Protective anti-HIV immune responses in non-human primates through DMA immunization. J. Med. Primatol. 25: 242–250.
Wang, B., Ugen, K.E., Srikantan, V., Agadjanyan, M.G., Dang, K., Refaefi, Y. et al. 1993 Gene inoculation generates immune responses against human immunodeficiency virus type 1. Proc. Natl. Acad. Sci. USA 90: 4156–4160.
Wang, B., Boyer, J.D., Ugen, K.E., Srikantan, V., Ayyavoo, V., Agadjanyan, M.G. et al. 1995 Nucleic acid-based immunization against HIV-1: induction of protective in vivo immune responses. AIDS 9: S159–170.
Tang, D., DeVrt, M. and Johnston, S. 1992 Genetic immunization is a simple method for elicting an immune response. Nature 356: 152–154.
Utmer, J., Donneily, J., Parker, S.E., Rhodes, G.H., Feigner, P.L., Dwarki, V.L. et al. 1993 Heterologous protection against influenza by injection of DMA encoding a viral protein. Science 259: 1745–1749.
Davis, H., Michel, M.L. and Whalen, R.G. 1993 DMA-based immunization induces continuous secretion of hepatitis B surface antigen and high levels of circulating antibody. Human Mol. Genetics 2: 1857–1851.
Fynan, E., Webster, R., Fuller, D., Haynes, J., Santoro, J. and Robinson, H. 1993 DMA vaccines: Protective immunizations by parenteral, mucosal, and gene-gun inoculations. Proc. Nati. Acad. Sci. USA 90: 11478–11482.
Margolis, H.S. 1993 Prevention of acute and chronic liver disease through immunization: hepatitis Band beyond. J.lnf.Dis. 168: 9–14.
Zarozinski, C.C., Fynan, E.F., Selin, L.K., Robinson, H.L. and Welsh, R.M. 1995 Protective CTL-dependent immunity and enhanced immunopathology in mice immunized by particle bombardment with DMA encoding an internal virion protein. J. Immunol. 154: 4010–4017.
Doe, B., Selby, M., Barnett, S., Baenzinger, J. and Walker, C.M. 1996 Induction of cytotoxic T-lymphocytes by intramuscular immunization with plasmid DMA is facilitated by bone marrow-derived cells. Proc. Natl. Acad. Sci. USA 93: 8578–8583.
Corr, M., Lee, D.J., Carson, D.A. and Tighe, H. 1996 Gene vaccination with naked plasmid DNA: mechanism of CTL priming. J. Exp. Med. 184: 1555–1560.
Pardoll, D.M. and Beckerteg, A.M. 1995 Exposing the immunology of naked DNA vaccines. Immunity 3: 165–169.
Brodsky, F.M. and Guagliardi, L.E. 1991 The cell biology of antigen processing and presentation. Ann. Rev. Immunol. 9: 707–744.
Wolff, J.A., Malone, R.W., Williams, R., Chong, W., Acsadi, G., Jani, A. and Feigner, P.L. 1990 Direct gene transfer into mouse muscle in vivo. Science 247: 1465–1468.
Beauchamp, J.R., Abraham, D.J., Bou-Gharios, G., Partridge, T.A. and Olsen, I. 1992 Expression and function of heterotypic adhesion molecules during differentiation of human skeletal muscle in culture. Am. J. Pathol. 140: 387–401.
Blau, H.M. and Webster, C. 1981 Isolation and characterization of human muscle cells. Proc. Nati. Acad. Sci. USA 78: 5623–5627.
Goebels, N., Michaelis, D., Wekerte, M. and Hohlfeld, R. 1992 Human myoblasts as antigen-presenting cells. J. Immunol. 148: 661–667.
Hohlfeld, R. and Engel, A.G. 1990 Induction of HLA-DR expression on human myoblasts with interferon-gamma. Am. J. Pathol. 136: 503–508.
Hohlfeld, R. and Engel, A.G. 1994 The immunobiology of muscle. Immunol. Today 15: 269–274.
Michaelis, D., Goebels, N. and Hohlfeld, R. 1993 Constitutive abd cytokine-induced expression of human leukocyte antigens and cell adhesion molecules by human myotubes. Am. J. Pathol. 143: 1142–1149.
Mantegazza, R., Hughes, S.M. Mitchell, D., Travis, M., Blau, H.M. and Steinman, L. 1991 Modulation of MHC class II antigen expression in human myoblasts after treatment with IFN-y. Neurol. 41: 1128–1132.
Roy, R., Dansereau, G. Tremblay, J.R., Belles-Isles, M., Huard, J., Labrecque, C. and Bouchard, J.R. 1991 Expression of major histocompatibility complex antigens on human myoblasts. Trans. Proceed. 23: 799–801.
June, C., Bluestone, J.A., Nadler, L.M. and Thompson, C.B. 1994 The B7 and CD28 receptor families. Immunol. Today 15: 321–333.
Lanier, L.L., O'Falton, S., Somoza, C., Phillips, J.H., Linsley, P.S., Okumura, K. et al. 1995 CD80 (B7) and CD86 (B70) provide similar costimulatory signals for T-cell proliferation, cytokine production, and generation of CTL. J. Immunol. 154: 97–105.
Linsley, P.S., Clark, E.A. and Ledbetter, J.A. 1990 The T-cell antigen, CD28, mediates adhesion with B cells by interacting with activation antigen, B7/BB-1. Proc. Natl. Acad. Sci. USA 87: 5031–5035.
Yang, Y., Su, Q., Grewal, I.S. Schilz, R., Flavell, R.A. and Wilson, J.M. 1996 Transient subversion of CD40 ligand function diminishes immune responses to adenovirus vectors in mouse liver and lung tissues. J. Virol. 70: 6370–6377.
Takahashi, H., Nakagawa, Y., Pendleton, C.D., Houghten, R.A., Yokomuro, K., Germain, R.N. and Berzofsky, J.A. 1992 Induction of broadly cross-reactive cytotoxic T cells recognizing an HIV-1 envelope determinant. Science 255: 333–336.
Shirai, M., Pendleton, C.D. and Berzofsky, J.A. 1992 Broad recognition of cytotoxic T-cell epitopes from the HIV-1 envelope protein with multiple class I histocompatibility molecules. J. Immunol. 148: 1657–1667.
Wang, B., Merva, M., Dang, K., Ugen, K.E., Boyer, J.D., Williams, W.V. and Weiner, D.B. 1994 DNA inoculation induces protective in vivo immune responses against cellular challenge with HIV-1 antigen-expressing cells. AIDS Res. and Hum. Retro. 10: S35–41.
Kundig, T.M., Bachmann, M.F., DiPaolo, C., Simard, J.J.L., Battegay, M., Lother, H. et al. 1995 Fibroblasts as efficient antigen-presenting cells in lymphoid organs. Science 268: 1343–1347.
Conry, R.M., Widera, G., LoBuglio, A.F., Fuller, J.T., Moore, S.E., Barlow, D.L. et al. 1996 Selected strategies to augment polynucleotide immunization. Gene Therapy 3: 67–74.
Wu, T.-C., Huang, A.Y.C., Jaffee, E.M., Levitsky, H.I. and Pardoll, D.M. 1995 A reassessment of the role of B7-1 expression in turner rejection. J. Ex. Med. 182: 1415–1421.
Huang, A.Y.C., Bruce, A.T., Pardoll, D.M. and Levitsky, H.I. 1996 Does B7-1 expression confer antigen-presenting cell capacity to tumors in vivo? J. Ex. Med. 183: 769–776.
Huang, A.Y.C., Golumbek, R., Ahmadzadeh, M., Jaffee, E., Pardoll, D.M. and Levitsky, H.I. 1994 Role of bone marrow-derived cells in presenting MHC class l-restricted tumor antigens. Science 264: 961–965.
Kuchroo, V.K., Das, M.R., Brown, J.A., Ranger, A.M., Zamvil, S.S., Sobel, R A et al. 1995 B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: application to sutoimrnune disease therapy. Cell 80: 707–718.
Azuma, M., Ito, D., Yagita, H., Okumura, K., Phillips, J.H., Lanier, L.L. and Somoza, C. 1993 B70 antigen is a second ligand for CTLA-4 and CD28. Nature 366: 76–79.
Freedman, A.S., Freeman, G.J., Rhynhart, K. and Nadler, L.M. 1991 Selective induction of B7/BB-1 on interferon-g-stimulated monocytes: a potential mechanism for amplification of T-cell activation through the CD28 pathway. Cell. Immunol. 137: 429–437.
Larsen, C.R., Ritchie, S.C., Hendrix, R., Linsley, P.S., Hathcock, K.S., Hodes, R.J. et al. 1994 Regulation of immunostimulatory function and costimulatory molecule (B7-1 and B7-2) expression on murine dedritic cells. J. Immunol. 152: 5208–5219.
Stack, R.M., Lenschow, D.J., Gray, G.S., Bluestone, J.A. and Fitch, F.W. 1994 IL-4 treatment of small splenic B cells induces costimulatory molecules B7-1 and B7-2. J. Immunol. 152: 5723–5733.
Linsley, P.S.W.B., Grosmaire, L.S., Aruffo, A., Damle, N.K. and Ledbetter, J.A. 1991 Binding of the B cell activation antigen B7 to CD28 costimulates T-cell proliferation and interieukin-2 mRNA accumulation. J. Exp. Med. 173: 721–730.
Azuma, M., Cayabyab, M., Buck, D., Phillips, J.H. and Lanier, L.L. 1992 CD28 interaction with B7 costimulates primary aJlogeneic proliferative responses and cytotoxicity mediated by small, resting T-lymphocytes. J. Exp. Med. 175: 353–360.
Levy, D.N., Fernandes, L.S., Williams, W.V. and Weiner, D.B. 1993 Induction of cell differentiation by human immunodeficiency virus 1 vpr. Cell 72: 541–550.
Agadjanyan, M.A. and Sidorova, E.V. 1991 Rote of antigen-binding B-lymphocytes in the formation of antigen-dependent. Biomed Science 2: 361–366.
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Kirn, J., Bagarazzi, M., Trivedi, N. et al. Engineering of in vivo immune responses to DNA immunization via codelivery of costimulatory molecule genes. Nat Biotechnol 15, 641–646 (1997). https://doi.org/10.1038/nbt0797-641
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DOI: https://doi.org/10.1038/nbt0797-641
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