| RRC ID |
52555
|
| 著者 |
Hanagata N, Li X, Chen MH, Li J, Hattori S.
|
| タイトル |
Double-stranded phosphodiester cytosine-guanine oligodeoxynucleotide complexed with calcium phosphate as a potent vaccine adjuvant for activating cellular and Th1-type humoral immunities.
|
| ジャーナル |
Int J Nanomedicine
|
| Abstract |
Conventional class B cytosine-guanine (CpG) (CpG-B) oligodeoxynucleotide (ODNs) consisting of a single-stranded (ss) phosphorothioate (PT) backbone (ss CpG-B-PT) is converted from a proinflammatory cytokine inducer to a type-I interferon (IFN) inducer when complexed with cationic materials. In this study, we designed ss CpG-B and double-stranded (ds) CpG-B ODNs with a phosphodiester (PD) backbone (ss CpG-B-PD and ds CpG-B-PD, respectively) that became type-I IFN inducers upon complexation with Lipofectamine 2000 (Lipo), a cationic liposome. The ds CpG-B-PD complex induced higher IFN-β expression in mouse macrophage-like RAW264 cells than ss CpG-B-PD and ss CpG-B-PT complexes. The fold induction of IFN-β increased with the number of CpG motifs in ds CpG-B-PD, and a complex of ds CpG-B-PD consisting of 72 base pairs with nine CpG motifs (ds CpG-B72-PD) and Lipo showed the highest capacity to induce IFN-β. The materials and method used for complexation influenced the degree of IFN-β induction: ds CpG-B72-PD entrapped by calcium phosphate (CaP) (ds CpG-B72-PD/CaP) showed a higher induction capacity than ds CpG-B72-PD adsorbed onto the CaP surface. Entrapment of ds CpG-B72-PD by CaP also enhanced the induction of the proinflammatory cytokine interleukin-12. Vaccinating mice with ds CpG-B72-PD/CaP in conjunction with ovalbumin (OVA) increased the ratios of OVA-specific CD8+ T cells to total CD8+ T cells in peripheral blood and of OVA-specific IgG2a associated with helper T (Th)1 cells to OVA-specific IgG1 associated with Th2 cells. These results indicate that ds CpG-B72-PD/CaP is an effective vaccine adjuvant that can activate both cellular and Th1-type humoral immune responses.
|
| 巻・号 |
13
|
| ページ |
43-62
|
| 公開日 |
2017-12-20
|
| DOI |
10.2147/IJN.S152141
|
| PII |
ijn-13-043
|
| PMID |
29317815
|
| PMC |
PMC5743182
|
| MeSH |
Adjuvants, Immunologic / chemistry*
Adjuvants, Immunologic / pharmacology*
Animals
CD8-Positive T-Lymphocytes / drug effects
CD8-Positive T-Lymphocytes / immunology
Calcium Phosphates / chemistry
Cell Line
Drug Delivery Systems / methods
Immunity, Humoral / drug effects*
Immunoglobulin G / blood
Interferon-beta / genetics
Interferon-beta / metabolism
Interleukin-12 / blood
Liposomes / administration & dosage
Liposomes / chemistry
Mice
Mice, Inbred C57BL
Oligodeoxyribonucleotides / chemistry
Oligodeoxyribonucleotides / immunology
Oligodeoxyribonucleotides / pharmacology*
Ovalbumin / immunology
Ovalbumin / pharmacology
Th1 Cells / drug effects
Th1 Cells / immunology*
Vaccines / immunology
|
| IF |
5.115
|
| 引用数 |
0
|
| リソース情報 |
| ヒト・動物細胞 |
RAW 264(RCB0535)
L929(RCB1451) |
