Determination of immune stimulatory properties of synthetic CpG oligodeoxynucleotide / cationic peptide complexest


Thesis Type: Postgraduate

Institution Of The Thesis: Middle East Technical University, Faculty of Arts and Sciences, Department of Biology, Turkey

Approval Date: 2012

Thesis Language: English

Student: Bilgi Güngör

Consultant: MAYDA GÜRSEL

Abstract:

Synthetic CpG containing oligodeoxynucleotides (ODNs) are recognized by Toll like Receptor 9 (TLR9) and induce a strong pro-inflamatory immune response. To date, four different CpG ODN classes have been described. K-Class ODNs (also known as B-ODN) are potent B cell activators and stimulate TNF secretion from plasmacytoid dendritic cells (pDC). D-Class ODNs (also known as A-ODNs) are the strongest stimulators of IFNa but suffer from GMP production problems through formation of undesirable multimeric structures, preventing their entry into clinical trials. In our study, conventional K-ODNs and cationic peptides TAT (+8) and LL37 (+6) were self-assembled to form nanoparticles. In contrast to free ODN, nanoparticles of sufficient stability stimulate IFNα production from both human and mouse cells. CpG ODN/peptide complexes were also shown to be good adjuvant candidates for vaccines in mouse and provide longer lasting immunity and better protection against a viral disease.