Development of CpG-Oligodeoxynucleotides for effective activation of rabbit TLR9 mediated immune responses
Journal
PLoS ONE
Journal Volume
9
Journal Issue
9
Date Issued
2014
Author(s)
Chuang, Tsung-Hsien
Lai, Chao-Yang
Tseng, Ping-Hui
Yuan, Chiun-Jye
Ploegh, Hidde L.
Abstract
CpG-oligodeoxynucleotides (CpG-ODN) are potent immune stimuli being developed for use as adjuvants in different species. Toll-like receptor 9 (TLR9) is the cellular receptor for CpG-ODN in mammalian cells. The CpG-ODN with 18-24 deoxynucleotides that are in current use for human and mouse cells, however, have low activity with rabbit TLR9. Using a cell-based activation assay, we developed a type of CpG-ODN containing a GACGTT or AACGTT motif in 12 phosphorothioate-modified deoxynucleotides with potent stimulatory activity for rabbit TLR9. The developed CpG-ODN have higher activities than other developed CpG-ODN in eliciting antigen-nonspecific immune responses in rabbit splenocytes. When mixed with an NJ85 peptide derived from rabbit hemorrhagic disease virus, they had potent activities to boost an antigen-specific T cell activation and antibody production in rabbits. Compared to Freund's adjuvant, the developed CpG-ODN are capable of boosting a potent and less toxic antibody response. The results of this study suggest that both the choice of CpG-motif and its length are important factors for CpG-ODN to effectively activate rabbit TLR9 mediated immune responses. Copyright: ? 2014 Chuang et al.
SDGs
Other Subjects
adenine; CpG oligodeoxynucleotide; cytosine; guanine; NJ85 peptide; phosphorothioic acid; thymine; toll like receptor 9; unclassified drug; virus protein; CPG-oligonucleotide; cytokine; immunoglobulin M; immunological adjuvant; oligodeoxyribonucleotide; peptide; phosphate; phosphorodithioic acid; toll like receptor 9; adjuvant therapy; animal cell; antibody production; antigen specificity; Article; controlled study; drug efficacy; drug potency; drug safety; immunostimulation; Lagovirus; mouse; nonhuman; nucleotide motif; spleen cell; T lymphocyte activation; toxicity testing; animal; chemistry; drug effects; HEK293 cell line; human; immunology; lymphocyte activation; metabolism; nucleotide sequence; rabbit; Rabbit hemorrhagic disease virus; spleen; T lymphocyte; Oryctolagus cuniculus; Adjuvants, Immunologic; Animals; Antibody Formation; Base Sequence; Cytokines; HEK293 Cells; Hemorrhagic Disease Virus, Rabbit; Humans; Immunoglobulin M; Lymphocyte Activation; Oligodeoxyribonucleotides; Peptides; Phosphates; Rabbits; Spleen; T-Lymphocytes; Toll-Like Receptor 9
Type
journal article