TLR9 recognises non-methylated cytosine-guanosine (CpG) motifs over-represented in bacterial or viral DNA and initiates pro-inflammatory signaling cascades. Synthetic CpG oligonucleotide (ODN) are agonists for TLR9 and have been exploited as adjuvants in preclinical models and clinical trials. We have previously shown that the dendritic cell receptor DEC-205 captures, internalizes and delivers CpG ODN to the late endosomes, which contain TLR9. Here we characterize the molecular basis underpinning the binding of CpG ODN to DEC-205 and identify the core motif required for this interaction. Given that efficient uptake of CpG ODN is a prerequisite for interaction with TLR9, we reasoned that designing ODN that contain the optimal motif for binding DEC-205 should make such CpG ODN superior adjuvants. Thus, utilizing the optimal DEC-205 binding motif, we designed a CpG ODN that efficiently bound DEC-205 but also contained the optimal motif for the stimulation TLR9. We provide proof-of-concept that such an ODN is a superior adjuvant, describe its stimulatory properties and unveil its unexpected propensity to drive the development of tissue resident memory cells.