Oligodesoxynucleotides as adjuvants: Use in prophylactic and therapeutic vaccines

• Applicant: Professor Dr. Klaus Michael Heeg
• Subject Area: Immunology
• Term: from 2005 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5443046

Immunostimulatory CpG DNA has attracted attention due to its potential use as vaccine adjuvant. Central goal of this application is to further elucidate the mechanisms of uptake and receptor binding of CpG DNA in innate immune cells. CpG DNA is recognized through a TLR9-dependent recognition complex in a two step process. DNA is first taken up into endosomes by multiple mechanisms and degraded there. In a second step fragments of DNA trigger TLR-9 dependent signaling within the endosome. We hypothesize that DNA, independent of its origin, can be immunostimulative provided it enters the endosomal compartment. To this various strategies will be utilized to target bacterial and mammalian DNA into endosomes. From our previous work on the structure/function relationship of synthetic oligonucleotides (ODN) we have developed a minimal model of DNA recognition by the TLR9-dependent complex. Using designed ODN and fragments of genomic DNA that were produced under controlled conditions we want to further characterize the active DNA structures and fragments, respectively. Finally we want to elucidate the molecular mechanism of inhibition of CpG recognition by poly-guanosine rich ODN. These experiments will add new information on the structure/function relationship of immunostimulatory DNA and will give new insights to tailor immunostimulatory DNA preparations or synthetic ODN fo the use as adjuvant.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1089: Novel Vaccination Strategies