The present invention provides highly active cyclic-di-nucleotide (CDN) immune stimulators that activate DCs via a recently discovered cytoplasmic receptor known as STING (Stimulator of Interferon Genes). In particular, the CDNs of the present invention are provided in the form of a composition comprising one or more cyclic purine dinucleotides induce STING-dependent type I interferon production, wherein the cyclic purine dinucleotides present in the composition are substantially pure 2&prime,5&prime,2&prime,5&prime and 2&prime,5&prime,3&prime,5&prime CDNs, and preferably Rp,Rp stereosiomers thereof.
