A Palindromic CpG-Containing Phosphodiester Oligodeoxynucleotide as a Mucosal Adjuvant Stimulates Plasmacytoid Dendritic Cell-Mediated T.sub.H1 Immunity

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 c...

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Published inPloS 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
LanguageEnglish
Published Public Library of Science 24.02.2014
Subjects
Cytokines
Dendritic cells
House mouse
Immunoglobulin A
Immunoglobulin G
Oligodeoxynucleotides
Vaccination
Vaccines
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Summary: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 T.sub.H 1 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. T.sub.H 1 and T.sub.H 2 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. G9.1 exhibited stronger IFN-[alpha]-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 T.sub.H 1, but not T.sub.H 2, -type Abs depended completely on pDCs, the first in vivo demonstration by CpG ODNs. G9.1 is a promising mucosal adjuvant for induction of pDC-mediated T.sub.H 1 immunity.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0088846