A Palindromic CpG-Containing Phosphodiester Oligodeoxynucleotide as a Mucosal Adjuvant Stimulates Plasmacytoid Dendritic Cell-Mediated TH1 Immunity

• Published in: PloS one Vol. 9; no. 2; p. e88846
• Main Authors: Maeyama, Jun-ichi, Takatsuka, Hisakazu, Suzuki, Fumiko, Kubota, Ayumi, Horiguchi, Satomi, Komiya, Takako, Shimada, Ichiroh, Murata, Eri, Osawa, Youko, Kitagawa, Harukazu, Matsuki, Takasumi, Isaka, Masanori, Yamamoto, Saburo, Iho, Sumiko
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 24.02.2014
• Subjects: Adjuvanticity; Adjuvants; Antigens; Bacteria; Biodegradation; Biology; BLyS protein; Bone marrow; Cell-mediated immunity; Clinical trials; CpG islands; Dendritic cells; Deoxyribonucleic acid; Diphtheria; DNA; Education; Forensic medicine; GATA-3 protein; Immune response; Immunity; Immunoglobulin A; Immunoglobulin E; Immunoglobulin G; Immunoglobulins; Infectious diseases; Interferon; Intranasal administration; Laboratories; Legal medicine; Leukocytes (mononuclear); Life sciences; Lymphocytes T; Medical research; Medicine; Mice; Mucosa; Mucosal immunity; Nuclease; Oligonucleotides; Otolaryngology; Peripheral blood mononuclear cells; Phosphorothioate; Rodents; T cell receptors; Tropical diseases; Vaccination; Vaccines; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0088846

Background CpG oligodeoxynucleotides (ODNs), resembling bacterial DNA, are currently tested in clinical trials as vaccine adjuvants. They have the nuclease-resistant phosphorothioate bond; the immune responses elicited differ according to the CpG ODN sequence and vaccination method. To develop a CpG ODN that can induce plasmacytoid dendritic cell (pDC)-mediated TH1 immunity through the mucosa, we constructed phosphodiester G9.1 comprising one palindromic CpG motif with unique polyguanosine-runs that allows degradation similar to naturally occurring bacterial DNA. Methods TH1 and TH2 immunity activation was evaluated by cytokine production pattern and T-bet/GATA-3 ratio in human peripheral blood mononuclear cells and mouse bone marrow cells. Adjuvanticity was evaluated in mice administered G9.1 with diphtheria toxoid (DT) through nasal vaccination. Results G9.1 exhibited stronger IFN-α-inducing activity than A-class CpG ODN2216 and increased T-bet/GATA-3 ratio by enhancing T-bet expression. Nasally administered G9.1 plus DT induced DT-specific mucosal IgA and serum IgG, but not IgE, responses with antitoxin activity in C57BL/6 and BALB/c mice, possibly due to IFN/BAFF production. Induction of TH1, but not TH2, -type Abs depended completely on pDCs, the first in vivo demonstration by CpG ODNs. Conclusions G9.1 is a promising mucosal adjuvant for induction of pDC-mediated TH1 immunity.