Immunostimulatory DNA-based vaccines reduce cytotoxic lymphocyte activity by a T-helper cell-independent mechanism

Hearn Jay Cho, Kenji Takabayashi, Pei Ming Cheng, Minh Duc Nguyen, Maripat Corr, Stephen Tuck, Eyal Raz

Research output: Contribution to journalArticlepeer-review

244 Scopus citations

Abstract

Immunostimulatory DNA sequences (ISS) contain unmethylated CpG dinucleotides within a defined motif. Immunization with ISS-based vaccines has been shown to induce high antigen-specific cytotoxic lymphocyte (CTL) activity and a T(h)1-biased immune response. We have developed a novel ISS- based vaccine composed of ovalbumin (OVA) chemically conjugated to ISS- oligodeoxynucleotide (ODN). Protein-ISS conjugate (PIC) is more potent in priming CTL activity and T(h)1-biased immunity than other ISS-based vaccines. Cytotoxic lymphocyte activation by ISS-ODN-based vaccines is preserved in both CD4(-/-) and MHC class II(-/-) gene-deficient animals. Furthermore, PIC provides protection against a lethal burden of OVA-expressing tumor cells in a CD8+ cell-dependent manner. These results demonstrate that PIC acts through two unique mechanisms: T-helper-independent activation of CTL and facilitation of exogenous antigen presentation on MHC class I. This technology may have clinical applications in cancer therapy and in stimulating host defense in AIDS and chronic immunosuppression.

Original languageEnglish
Pages (from-to)509-514
Number of pages6
JournalNature Biotechnology
Volume18
Issue number5
DOIs
StatePublished - May 2000
Externally publishedYes

Keywords

  • AIDS
  • CTL activation
  • CpG motif
  • Immunostimulatory DNA sequences

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