Conjugation of protein to immunostimulatory DNA results in a rapid, long-lasting and potent induction of cell-mediated and humoral immunity

Eur J Immunol. 2000 Jul;30(7):1939-47. doi: 10.1002/1521-4141(200007)30:7<1939::AID-IMMU1939>3.0.CO;2-#.


Immunostimulatory DNA sequences (ISS) are a potent Th1 adjuvant. We hypothesized that conjugation of ISS to protein antigens would strongly enhance their immunogenicity because both antigen and adjuvant (ISS) would be delivered to the same locale/antigen-presenting cell. To test this hypothesis, we conjugated a 22-mer immunostimulatory oligodeoxynucleotide (ISS-ODN) to two test antigens of differing intrinsic immunogenicity, namely Escherichia coli beta-galactosidase and the HIV-1 envelope glycoprotein gp120. We show that the antigen-ISS conjugates rapidly induce Th1 cells secreting high levels of IFN-gamma, strong CTL activity, and high titer IgG2a and HIV-neutralizing antibodies, exceeding gene and protein vaccination alone or immunization with mixtures of antigen and ISS-ODN. The data suggest that this procedure generates a novel and unique vaccine that rapidly triggers strong humoral and cell-mediated immunity.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Bacterial / blood*
  • Antibodies, Bacterial / immunology
  • Antibody Formation / immunology
  • CHO Cells
  • Cricetinae
  • Electrophoresis, Polyacrylamide Gel / methods
  • Escherichia coli / enzymology
  • Female
  • HIV Antibodies / blood*
  • HIV Antibodies / immunology
  • HIV Envelope Protein gp120 / genetics
  • HIV Envelope Protein gp120 / immunology*
  • Immunity, Cellular / immunology
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Interferon-gamma / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Oligodeoxyribonucleotides / immunology*
  • Plasmids / immunology
  • Sodium Dodecyl Sulfate
  • T-Lymphocytes, Cytotoxic / immunology*
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Thionucleotides / immunology*
  • Time Factors
  • beta-Galactosidase / genetics
  • beta-Galactosidase / immunology*


  • Antibodies, Bacterial
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • Immunoglobulin G
  • Oligodeoxyribonucleotides
  • Thionucleotides
  • Sodium Dodecyl Sulfate
  • Interferon-gamma
  • beta-Galactosidase