title: Adjuvanticity of a CTLA-4 3' UTR complementary oligonucleotide for emulsion formulated recombinant subunit and inactivated vaccines.
abstract: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is recognized as a critical inhibitory regulator of T-cell proliferation and activation, opposing the action of CD28-mediated co-stimulation. Interfering or blocking CTLA-4 can result in continuous T-cell activation required for the full immune response to pathogenic microbes and vaccines. To test if nucleic acid-based CTLA-4 inhibitors could be developed into a novel adjuvant, we designed two oligonucleotides, CMD-1 and CMD-2, with the sequences complementary to the conserve regions identical between human and mouse CTLA-4 mRNA 3' untranslated region (3' UTR), and tested their in vitro effects on CTLA-4 production and their adjuvanticity for vaccines in mice. We found that CMD-1 inhibited the antigen-induced CTLA-4 up-regulation on the CD4+T cells by interfering its mRNA expression, maintained higher levels of CD80 and CD86 on the CD11c+cells and promoted the recalled proliferation of the CD4+T cells and CD19+B cells, and that the CMD-1 enhanced the antibody response against recombinant PCV2b capsid protein or inactivated foot-and-mouth disease virus in both ICR and BALB/c mice. These data suggest that the CMD-1 could be used as a novel vaccine adjuvant capable of inhibiting inhibitory signals rather than inducing stimulatory signals of immune cells.
authors.affiliation: Department of Molecular Biology, College of Basic Medical Sciences, Norman Bethune Health Science Center, Jilin University, Changchun 130021, Jilin, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Molecular Biology, College of Basic Medical Sciences, Norman Bethune Health Science Center, Jilin University, Changchun 130021, Jilin, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Molecular Biology, College of Basic Medical Sciences, Norman Bethune Health Science Center, Jilin University, Changchun 130021, Jilin, China.
authors.forename: Peiyan
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Department of Molecular Biology, College of Basic Medical Sciences, Norman Bethune Health Science Center, Jilin University, Changchun 130021, Jilin, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Molecular Biology, College of Basic Medical Sciences, Norman Bethune Health Science Center, Jilin University, Changchun 130021, Jilin, China.
authors.forename: Fangjie
authors.initials: F
authors.lastname: Lu
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, Norman Bethune Health Science Center, Jilin University, Changchun 130021, Jilin, China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Tu
authors.affiliation: Department of Molecular Biology, College of Basic Medical Sciences, Norman Bethune Health Science Center, Jilin University, Changchun 130021, Jilin, China.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, Norman Bethune Health Science Center, Jilin University, Changchun 130021, Jilin, China.
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, Norman Bethune Health Science Center, Jilin University, Changchun 130021, Jilin, China. Electronic address: ylyu@jlu.edu.cn.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Molecular Biology, College of Basic Medical Sciences, Norman Bethune Health Science Center, Jilin University, Changchun 130021, Jilin, China. Electronic address: wlying@jlu.edu.cn.
authors.forename: Liying
authors.initials: L
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors* / Q000235:genetics; D004655:Emulsions / Q000008:administration & dosage; D005260:Female; D029544:Foot-and-Mouth Disease Virus / Q000276:immunology*; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D009841:Oligonucleotides / Q000008:administration & dosage*; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D020413:3' Untranslated Regions; D000276:Adjuvants, Immunologic; D060908:CTLA-4 Antigen; D004655:Emulsions; D009841:Oligonucleotides; D014612:Vaccines; D015164:Vaccines, Inactivated; D022223:Vaccines, Subunit
keywords: 3′ UTR; Adjuvant; CTLA-4; Oligonucleotide; Vaccine