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

Immunostimulatory DNA sequences (ISS) contain unmethylated CpG dinucleotide s within a defined motif. Immunization with ISS-based vaccines has been sho wn 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-oligodeoxynucleot ide (ODN). Protein-ISS conjugate (PIC) is more potent in priming CTL activi ty and T(h)1-biased immunity than other ISS-based vaccines. Cytotoxic lymph ocyte activation by ISS-ODN-based vaccines is preserved in both CD4(-/-) an d MHC class II-/- gene-deficient animals. Furthermore, PIC provides protect ion against a lethal burden of OVA-expressing tumor cells in a CD8(+) cell- dependent manner. These results demonstrate that PIC acts through two uniqu e mechanisms: T-helper-independent activation of CTL and facilitation of ex ogenous antigen presentation on MHC class I. This technology may have clini cal applications in cancer therapy and in stimulating host defense in AIDS and chronic immunosuppression.