Abstract
A priority in current vaccine research is the development of multivalent vaccines that support the efficient priming of long-lasting CD8+ T-cell immunity. We developed a novel vaccination strategy that used synthetic, cationic (positively charged), and antigenic peptides complexed to negatively charged nucleic acids: antigenic, major histocompatibility complex-class I-binding epitopes fused with a cationic sequence derived from the HIV tat protein (tat50–57: KKRRQRRR) were mixed with nucleic acids (e.g., CpG-containing oligonucleotides) to quantitatively form peptide/nucleic acid complexes. The injection of these complexes efficiently primed long-lasting, specific CD8+ T-cell immunity of high magnitude. This chapter describes a novel strategy to codeliver complexes of cationic/antigenic peptides bound to antigen-encoding plasmid DNA vaccines in a way that enhances the immunogenicity of both components for T cells.
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References
Gurunathan, S., Klinman, D. M., and Seder, R. A. (2000) DNA vaccines: immunology, application and optimization. Annu. Rev. Immunol. 18, 927–974.
Mahvi, D. M., Sheehy, M. J., and Yang, N. S. (1997) DNA cancer vaccines: a gene gun approach. Immunol. Cell Biol. 75, 456–460.
Prayaga, S. K., Ford, M. J., and Haynes, J. R. (1997) Manipulation of HIV-1 gp120-specific immune responses elicited via gene gun-based DNA immunization. Vaccine 15, 1349–1352.
Torres, C. A., Iwasaki, A., Barber, B. H., and Robinson, H. L. (1997) Differential dependence on target site tissue for gene gun and intramuscular DNA immunizations. J. Immunol. 158, 4529–4532.
Macklin, M. D., McCabe, D., McGregor, M. W., et al. (1998) Immunization of pigs with a particle-mediated DNA vaccine to influenza A virus protects against challenge with homologous virus. J. Virol. 72, 1491–1496.
Cho, J. H., Youn, J. W., and Sung, Y. C. (2001) Cross-priming as a predominant mechanism for inducing CD8+ T cell responses in gene gun DNA immunization. J. Immunol. 167, 5549–5557.
Ulmer, J. B., DeWitt, C. M., Chastain, M., et al (1999) Enhancement of DNA vaccine potency using conventional aluminum adjuvants. Vaccine 18, 18–28.
Wang, S., Liu, X., Fisher, K., et al. (2000) Enhanced type I immune response to a hepatitis B DNA vaccine by formulation with calcium-or aluminum phosphate. Vaccine 18, 1227–1235.
Kwissa, M., Lindblad, E. B., Schirmbeck, R., and Reimann, J. (2003) Codelivery of a DNA vaccine and a protein vaccine with aluminum phosphate stimulates a potent and multivalent immune response. J. Mol. Med. 81, 502–510.
Leonetti, J. P., Degols, G., and Lebleu, B. (1990) Biological activity of oligonucleotide-poly(L-lysine) conjugates: mechanism of cell uptake. Bioconjug. Chem. 1, 149–153.
Midoux, P., Mendes, C., Legrand, A., et al. (1993). Specific gene transfer mediated by lactosylated poly-L-lysine into hepatoma cells. Nucleic Acids Res. 21, 871–878.
Murray, K. D., Etheridge, C. J., Shah, S. I., et al. (2001) Enhanced cationic liposome-mediated transfection using the DNA-binding peptide mu (mu) from the adenovirus core. Gene Ther. 8, 453–460.
Futaki, S. (2002) Arginine-rich peptides: potential for intracellular delivery of macromolecules and the mystery of the translocation mechanisms. Int. J. Pharm. 245, 1–7.
Lindsay, M. A. (2002) Peptide-mediated cell delivery: application in protein target validation. Curr. Opin. Pharmacol. 2, 587–594.
Ye, D., Xu, D., Singer, A. U., and Juliano, R. L. (2002) Evaluation of strategies for the intracellular delivery of proteins. Pharm. Res. 19, 1302–1309.
Leifert, J. A., Harkins, S., and Whitton, J. L. (2002) Full-length proteins attached to the HIV tat protein transduction domain are neither transduced between cells, nor exhibit enhanced immunogenicity. Gene Ther. 9, 1422–1428.
Riedl, P., Stober, D., Oehninger, C., Melber, K., Reimann, J., and Schirmbeck, R. (2002) Priming Th1 immunity to viral core particles is facilitated by trace amounts of RNA bound to its arginine-rich domain. J. Immunol. 168, 4951–4959.
Riedl, P., Buschle, M., Reimann, J., and Schirmbeck, R. (2002) Binding immune-stimulating oligonucleotides to cationic peptides from viral core antigen enhances their potency as adjuvants. Eur. J. Immunol. 32, 1709–1716.
Schirmbeck, R., Riedl, P., Zurbriggen, R., Akira, S., and Reimann, J. (2003) Antigenic epitopes fused to cationic peptide bound to oligonucleotides facilitate toll-like receptor 9-dependent, but CD4+ T cell help-independent, priming of CD8+ T cells. J. Immunol. 171, 5198–5207.
Riedl, P., Reimann, J., and Schirmbeck, R. (2004) Peptides containing antigenic and cationic domains have enhanced, multivalent immunogenicity when bound to DNA vaccines. J. Mol. Med. 82, 144–152.
Buschle, M., Schmidt, W., Zauner, W., et al. (1997) Transloading of tumor antigen-derived peptides into antigen-presenting cells. Proc. Natl. Acad. Sci. USA 94, 3256–3261.
Schmidt, W., Buschle, M., Zauner, W., et al. (1997) Cell-free tumor antigen peptide-based cancer vaccines. Proc. Natl. Acad. Sci. USA 94, 3262–3267.
Mattner, F., Fleitmann, J. K., Lingnau, K., et al. (2002) Vaccination with poly-L-arginine as immunostimulant for peptide vaccines: induction of potent and long-lasting T-cell responses against cancer antigens. Cancer Res. 62, 1477–1480.
Schirmbeck, R., Böhm, W., Ando, K.-I., Chisari, F. V., and Reimann, J. (1995) Nucleic acid vaccination primes hepatitis B surface antigen-specific cytotoxic T lymphocytes in nonresponder mice. J. Virol. 69, 5929–5934.
Schirmbeck, R., Stober, D., El Kholy, S., Riedl, P., and Reimann, J. (2002) The immunodominant, Ld-restricted T cell response to hepatitis B surface antigen (HBsAg) efficiently suppresses T cell priming to multiple Dd-, Kd-, and Kb-restricted HBsAg epitopes. J. Immunol. 168, 6253–6262.
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Riedl, P., Reimann, J., Schirmbeck, R. (2006). Complexes of DNA Vaccines With Cationic, Antigenic Peptides Are Potent, Polyvalent CD8+ T-Cell-Stimulating Immunogens. In: Saltzman, W.M., Shen, H., Brandsma, J.L. (eds) DNA Vaccines. Methods in Molecular Medicine™, vol 127. Humana Press. https://doi.org/10.1385/1-59745-168-1:159
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DOI: https://doi.org/10.1385/1-59745-168-1:159
Publisher Name: Humana Press
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