Coimmunization with an optimized IL-15 plasmid results in enhanced function and longevity of CD8 T cells that are partially independent of CD4 T cell help

J Immunol. 2005 Jul 1;175(1):112-23. doi: 10.4049/jimmunol.175.1.112.


DNA vaccines are a promising technology for the induction of Ag-specific immune responses, and much recent attention has gone into improving their immune potency. In this study we test the feasibility of delivering a plasmid encoding IL-15 as a DNA vaccine adjuvant for the induction of improved Ag-specific CD8(+) T cellular immune responses. Because native IL-15 is poorly expressed, we used PCR-based strategies to develop an optimized construct that expresses 80-fold higher than the native IL-15 construct. Using a DNA vaccination model, we determined that immunization with optimized IL-15 in combination with HIV-1gag DNA constructs resulted in a significant enhancement of Ag-specific CD8(+) T cell proliferation and IFN-gamma secretion, and strong induction of long-lived CD8(+) T cell responses. In an influenza DNA vaccine model, coimmunization with plasmid expressing influenza A PR8/34 hemagglutinin with the optimized IL-15 plasmid generated improved long term CD8(+) T cellular immunity and protected the mice against a lethal mucosal challenge with influenza virus. Because we observed that IL-15 appeared to mostly adjuvant CD8(+) T cell function, we show that in the partial, but not total, absence of CD4(+) T cell help, plasmid-delivered IL-15 could restore CD8 secondary immune responses to an antigenic DNA plasmid, supporting the idea that the effects of IL-15 on CD8(+) T cell expansion require the presence of low levels of CD4 T cells. These data suggest a role for enhanced plasmid IL-15 as a candidate adjuvant for vaccine or immunotherapeutic studies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS Vaccines / genetics
  • AIDS Vaccines / immunology
  • AIDS Vaccines / pharmacology
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Cellular Senescence
  • Cloning, Molecular
  • Female
  • Genetic Vectors
  • HeLa Cells
  • Humans
  • Immunization
  • Immunologic Memory
  • In Vitro Techniques
  • Influenza Vaccines / genetics
  • Influenza Vaccines / immunology
  • Influenza Vaccines / pharmacology
  • Interferon-gamma / biosynthesis
  • Interleukin-15 / genetics*
  • Interleukin-15 / immunology*
  • Lymphocyte Activation
  • Lymphocyte Cooperation
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Plasmids
  • Transfection
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology
  • Vaccines, DNA / pharmacology


  • AIDS Vaccines
  • Influenza Vaccines
  • Interleukin-15
  • Vaccines, DNA
  • Interferon-gamma