CpG oligodeoxynucleotides (ODN) act as adjuvants that switch on T helper 1 (Th1) immunity. These synthetic ODN contain unmethylated CpG motifs, which induce macrophages to secrete IL-12, promoting IFN-γ secretion by NK cells. This cytokine environment favors Th1 differentiation. When coadministered with antigen, CpG ODN shift immune responses from Th2 to Th1, as seen in both BALB/c (Th2-biased) and B10.D2 (Th1-biased) mice. Immunization with HEL in IFA induced Th2 responses, but with IFA-HEL plus CpG ODN, Th1 responses were dominant, characterized by increased IFN-γ secretion and IgG2a production. CpG ODN also induced anti-HEL IgG2a, a Th1-associated isotype, while non-CpG ODN did not. CpG ODN are thus effective adjuvants for inducing Th1 immunity, which is crucial for protective responses against certain infections. They are safer than CFA, which is not suitable for human vaccines due to inflammatory side effects. CpG ODN can be used in human vaccines to elicit protective Th1 immunity. The mechanism involves CpG motifs in bacterial DNA, which activate innate immune cells and promote Th1 responses. CpG ODN are effective in both Th1- and Th2-biased mice, inducing Th1 responses without significant toxicity. This makes them promising candidates for future vaccines.CpG oligodeoxynucleotides (ODN) act as adjuvants that switch on T helper 1 (Th1) immunity. These synthetic ODN contain unmethylated CpG motifs, which induce macrophages to secrete IL-12, promoting IFN-γ secretion by NK cells. This cytokine environment favors Th1 differentiation. When coadministered with antigen, CpG ODN shift immune responses from Th2 to Th1, as seen in both BALB/c (Th2-biased) and B10.D2 (Th1-biased) mice. Immunization with HEL in IFA induced Th2 responses, but with IFA-HEL plus CpG ODN, Th1 responses were dominant, characterized by increased IFN-γ secretion and IgG2a production. CpG ODN also induced anti-HEL IgG2a, a Th1-associated isotype, while non-CpG ODN did not. CpG ODN are thus effective adjuvants for inducing Th1 immunity, which is crucial for protective responses against certain infections. They are safer than CFA, which is not suitable for human vaccines due to inflammatory side effects. CpG ODN can be used in human vaccines to elicit protective Th1 immunity. The mechanism involves CpG motifs in bacterial DNA, which activate innate immune cells and promote Th1 responses. CpG ODN are effective in both Th1- and Th2-biased mice, inducing Th1 responses without significant toxicity. This makes them promising candidates for future vaccines.