CpG-containing synthetic oligonucleotides promote B and cytotoxic T cell responses to protein antigen: a new class of vaccine adjuvants

Eur J Immunol. 1997 Sep;27(9):2340-4. doi: 10.1002/eji.1830270931.


Foreign DNA has been shown to impinge on immune cell function by an as yet unidentified mechanism. We and others have demonstrated that single-stranded (ss) DNA containing the motif CpG flanked by two 5' purines and two 3' pyrimidines are mitogenic for B cells and activate macrophages to release tumor necrosis factor-alpha, interferon-gamma, interleukin (IL)-6 or IL-12. Because of these pro-inflammatory responses we investigated if ssDNA would serve as a potential vaccine adjuvant. Here we show that CpG-containing oligonucleotides represent a powerful adjuvant for both humoral and cellular immune responses. When ssDNA was incorporated into inocula, specific antibody titers of the IgG2 isotype were enhanced by greater than 100-fold. Primary cytotoxic T lymphocyte responses generated to either unprocessed protein antigen or major histocompatibility complex class I-restricted peptide were exceedingly strong. Evidence is also provided that oligomers directly influenced T cell receptor-triggered T cell proliferation. Thus ssDNA oligomers may serve as inexpensive and safe vaccine adjuvants and, in addition, differential effects due to sequence may allow for directed responses.

MeSH terms

  • Adjuvants, Immunologic*
  • Animals
  • B-Lymphocytes / immunology*
  • Base Sequence
  • Cytotoxicity, Immunologic
  • DNA, Single-Stranded / immunology
  • Dinucleoside Phosphates / immunology*
  • Lymph Nodes / immunology
  • Lymphocyte Activation
  • Macrophages / immunology
  • Mice
  • Mice, Inbred C57BL
  • Oligodeoxyribonucleotides / immunology*
  • Ovalbumin / immunology
  • T-Lymphocytes / immunology*


  • Adjuvants, Immunologic
  • DNA, Single-Stranded
  • Dinucleoside Phosphates
  • Oligodeoxyribonucleotides
  • cytidylyl-3'-5'-guanosine
  • Ovalbumin