CpG oligodeoxynucleotides as mucosal adjuvants.
Bacterial DNA comprising palindromic sequences and containing unmethylated CpG is recognized by toll-like receptor 9 of plasmacytoid dendritic cells (pDCs) and induces the production of interferon-α and chemokines, leading to the activation of a Th1 immune response. Therefore, synthetic equivalents of bacterial DNA (CpG oligodeoxynucleotides) have been developed for clinical applications. They are usually phosphorothioated for in vivo use; this approach also leads to adverse effects as reported in mouse models.Mucosal vaccines that induce both mucosal and systemic immunity received substantial attention in recent years. For their development, phosphodiester-linked oligodeoxynucleotides, including the sequence of a palindromic CpG DNA may be advantageous as adjuvants because their target pDCs are present right there, in the mucosa of the vaccination site. In addition, the probability of adverse effects is believed to be low. Here, we review the discovery of such CpG oligodeoxynucleotides and their possible use as mucosal adjuvants.
a Host Defense Laboratory; Faculty of Medical Sciences; University of Fukui ; Yoshida-gun , Fukui , Japan.
Sumiko
S
Iho
Jun-ichi
J
Maeyama
Fumiko
F
Suzuki
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D058956:Administration, Mucosal; D000818:Animals; D003713:Dendritic Cells / Q000187:drug effects; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects*; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides
Ab, antibody; BCG, Mycobacterium bovis Bacillus Calmette-Guerin; CpG; DT, diphtheria toxoid; DTH, delayed-type hypersensitivity; G, guanine; IFN, interferon; IgG1; IgG2a/c; ODNs, oligodeoxynucleotides; PBMCs, peripheral blood mononuclear cells; PPD, purified protein derivative; TLR, toll-like receptor; Th1; mucosal adjuvant; pDC; pDCs, plasmacytoid dendritic cells; palindrome; phosphodiester; phylaxis; rCTB, recombinant cholera toxin B subunit; sIgA, secretory IgA; secretory IgA