Bacterial DNA contains unmethylated “CpG motifs” that strongly stimulate the mammalian immune system. Synthetic oligodeoxynucleotides (ODN) expressing CpG motifs patterned after those found in bacteria trigger cells of the immune system to proliferate, mature, and produce cytokines, chemokines and immnunoglobulin (Ig) Krieg et al., Nature 374:546, 1995; Yamamoto et al., J. Immunol. 148:407, 1992; Klinman et al., Proc. Natl. Acad. Sci. USA 93:2879, 1996; Takeshita et al., Cell Immunology 206:101, 2000). These immunostimulatory activities are being harnessed therapeutically. CpG ODN show promise as immune adjuvants, significantly improving the immune response to co-administered antigens (Roman et al., Nature Medicine 3:849, 1997; Davis et al., J. Immunol. 160:870, 1998; Chu et al., J. Exp. Med. 186:1623, 1997; Klinman et al., Springer Semin Immunopathol 22:173, 2000; Tighe et al., J Allergy Clin Immunol 106:124, 2000). The strong Th1 response elicited by CpG ODN down-regulates Th2 mediated IgE and cytokine production, thereby interfering with allergic asthma (Sur et al., J. Immunol. 162:6284, 1999; Broide et al., J. Immunol. 161:7054, 1998; Kline et al., J. Immunol. 160:2555, 1998). Finally, by pre-activating the innate immune system, CpG ODN can protect naive animals against a variety of microbial and parasitic pathogens (Krieg et al., J. Immunol. 161:2428, 1998; Elkins et al., J. Immunol. 162:2291, 1999; Klinman, Antisense awed Nuc Acid Drug Dev 8:181, 1998; Klinman et al., Infect Immun 67:5658, 1999; Klinman et al., Immunity 11:123, 1999).
Prolonging the bioavailability and duration of action of CpG ODN may improve their therapeutic efficacy. Unfortunately, phosphorothioate CpG ODN used in vivo are rapidly eliminated from the circulation due to adsorption onto serum proteins and degradation by serum nucleases (Litzinger et al., Biochim. Biophys. Acta 1281:139, 1996; Soni et al., Hepatology 28:1402, 1998; Gregoriadis, Pharm. Res 15:661, 1998). One potential method for protecting CpG ODN from degradation while increasing their uptake by cells of the immune system involves liposome encapsulation (MacDonald et al., Biochim. Biophys. Acta 1061:297, 1991; Takeshita et al., Eur. J. Immunol. 30:108, 2000).