Immunostimulatory DNA-based vaccines induce cytotoxic lymphocyte activity
by a T-helper cell-independent mechanism
Hearn Jay Cho1, Kenji Takabayashi1, Pei-Ming Cheng1, Minh-Duc Nguyen1, Maripat Corr1, Stephen Tuck2
& Eyal Raz1
1
Department of Internal Medicine and The Sam and Rose
Stein Institute for Research on Aging, University of California San Diego
, La Jolla, CA 92093-0663.
2
Dynavax Technologies Corp., 717 Potter
Street, Berkeley, CA 94710
Correspondence should be addressed to Eyal Raz eraz@usd.eduimmunostimulatory DNA sequencesCpG motifCTL activationAIDS
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
Th1-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 Th1-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.
