RRC ID 52555
Author Hanagata N, Li X, Chen MH, Li J, Hattori S.
Title Double-stranded phosphodiester cytosine-guanine oligodeoxynucleotide complexed with calcium phosphate as a potent vaccine adjuvant for activating cellular and Th1-type humoral immunities.
Journal 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.
Volume 13
Pages 43-62
Published 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
Times Cited 0
Human and Animal Cells RAW 264(RCB0535) L929(RCB1451)