CpG oligodeoxynucleotides as mucosal adjuvants

• Published in: Human vaccines & immunotherapeutics Vol. 11; no. 3; pp. 755 - 760
• Main Authors: Iho, Sumiko, Maeyama, Jun-ichi, Suzuki, Fumiko
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 2015
• Subjects: Ab, antibody; Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - pharmacology; Administration, Mucosal; Animals; BCG, Mycobacterium bovis Bacillus Calmette-Guerin; CpG; Dendritic Cells - drug effects; DT, diphtheria toxoid; DTH, delayed-type hypersensitivity; G, guanine; Humans; IFN, interferon; IgG1; IgG2a/c; Immunity, Mucosal - drug effects; mucosal adjuvant; ODNs, oligodeoxynucleotides; Oligodeoxyribonucleotides - administration & dosage; Oligodeoxyribonucleotides - pharmacology; palindrome; PBMCs, peripheral blood mononuclear cells; pDC; pDCs, plasmacytoid dendritic cells; phosphodiester; phylaxis; PPD, purified protein derivative; rCTB, recombinant cholera toxin B subunit; secretory IgA; sIgA, secretory IgA; Th1; TLR, toll-like receptor; DTH, delayed-type hypersensitivity; IFN, interferon; DT, diphtheria toxoid; rCTB, recombinant cholera toxin B subunit; Ab, antibody; IgG2a/c; pDCs, plasmacytoid dendritic cells; phylaxis; IgG1; ODNs, oligodeoxynucleotides; phosphodiester; sIgA, secretory IgA; pDC; G, guanine; palindrome; mucosal adjuvant; BCG, Mycobacterium bovis Bacillus Calmette-Guerin; PBMCs, peripheral blood mononuclear cells; CpG; Th1; secretory IgA; PPD, purified protein derivative; TLR, toll-like receptor
• ISSN: 2164-5515; 2164-554X
• DOI: 10.1080/21645515.2014.1004033

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.