Synthetic innate defense regulator peptide combination using CpG ODN as a novel adjuvant induces long­lasting and balanced immune responses.

ABSTRACT

Vaccines are critical tools for the prevention and treatment of several diseases. Adjuvants have been traditionally used to enhance immunity to vaccines and experimental antigens. In the present study, the adjuvant combination of CpG oligodeoxynucleotides (CpG ODN) and the innate defense regulator (IDR) peptide, IDR­HH2, was evaluated for its ability to enhance and modulate the immune response when formulated with alum and the recombinant hepatitis B surface antigen (HBsAg). The CpG­HH2 complex enhanced the secretions of tumor necrosis factor­α, monocyte chemotactic protein 1 and interferon­Î³ by human peripheral blood mononuclear cells and promoted murine bone marrow dentritic cell maturation. In addition, the present study demonstrated that IDR­HH2 was chemotactic for human neutrophils, THP­1 cells and RAW264.7 cells at concentrations between 2.5 and 40 µg/ml. The present study also observed that significantly higher anti­HBs antibody titers, which were sustained at high levels for as long as 35 weeks following the boost immunization, were induced by the combination adjuvant, even when co­administered with a commercial hepatitis B vaccine at a low antigen dose (0.1 µg HBsAg). Notably, the level of IgG2a was almost equal to the level of IgG1, indicating that a balanced T helper (Th)1/Th2 immune response was elicited by the novel vaccine, which was consistent with the ELISpot results. These data suggest that the CpG­HH2 complex may be a potential effective adjuvant, which facilitates a reduction in the dose of antigen and induces long­lasting, balanced immune responses.