Nucleic Acids Research, 2005, Vol. 33, No. 11 3557 Figure 4. Dose response in mice treated with CpG ODN fma1555 72 h post administration. Female Balb/c mice (3–6 mice/group) received CpG ODN 1555 or CpG ODN fma1555 (30, 100 or 300 mg/mouse) intraperitoneally. Splenocytes were collected 72 h after treatment. Shown in this figure are the numbers of cytokine and IgM secreting cells per 106 splenocytes. of CpG ODN fma1555 and the number of cytokine- and immunoglobulin-secreting cells in spleen. Mice treated with ODN fma1556 did not elicit cytokine secretion. CpG ODNs have been shown to activate the innate immune system to improve the clinical outcome in several infectious models. Speciﬁcally, studies assessing the immunoprotect- ive effects of CpG ODNs show that administration of CpG- containing DNA oligonucleotides alone (but not control oligonucleotides lacking CpG motifs) reduces the severity of an intradermal L.major challenge in mice when administered as early as three days prior to infection or as late as three weeks post infection (45). To assess the immunoprotective properties of CpG ODN fma1555, adult female Balb/c mice were challenged with live L.major metacyclic promastigotes intradermally in the ear and left either untreated or treated in situ with 25 mg of CpG ODN fma1555 or CpG ODN 1555 (Figure 5). As reported earlier, untreated Balb/c mice developed an ulcerative skin lesion that ultimately led to the loss of the outer ear 10 weeks after infection (40). In contrast, Balb/c mice that were treated with CpG ODN fma1555 or CpG ODN 1555 showed a signiﬁcant (P < 0.05) reduction in der- mal pathology by comparison to that of untreated mice, as assessed by one-way ANOVA. Although the lesions tended to be smaller in CpG ODN 1555-treated mice than in CpG ODN