title: CpG-C ISS-ODN activation of blood-derived B cells from healthy and chronic immunodeficiency virus-infected macaques.
abstract: Cytosine-phosphate-guanine class C (CpG-C) immunostimulatory sequence oligodeoxynucleotides (ISS-ODNs) activate human B cells and dendritic cells (DCs), properties that suggest potential use as a novel adjuvant to enhance vaccine efficacy. After demonstrating that the CpG-C ISS-ODN C274 activates macaque DCs, we examined in vitro activation of macaque B cells by C274 as a prelude to evaluation of this molecule as an adjuvant in the testing of candidate human immunodeficiency virus vaccines in the rhesus macaque-simian immunodeficiency virus (SIV) model. C274 induced macaque CD20(+) B cells to proliferate more strongly than CD40 ligand or CpG-B ISS-ODN. C274 enhanced B cell survival; increased viability was most evident after 3-7 days of culture. Increased expression of CD40, CD80, and CD86 by B cells was apparent within 24 h of exposure to C274 and persisted for up to 1 week. C274-stimulated, B cell-enriched and peripheral blood mononuclear cell suspensions from naïve and immunodeficiency virus-infected monkeys secreted several cytokines [e.g., interleukin (IL)-3, IL-6, IL-12, interferon-alpha] and chemokines [e.g., monocyte chemoattractant protein-1/CC chemokine ligand 2 (CCL2), macrophage-inflammatory protein-1alpha/CCL3, IL-8/CXC chemokine ligand 8]. In comparison, exposure of macaque B cells to SIV had minimal impact on surface phenotype, despite inducing cytokine and chemokine production in cells from infected and uninfected animals. These observations emphasize the need to identify strategies to optimally boost immune function, as immunodeficiency viruses themselves only partially activate B cells and DCs. The ability of C274 to stimulate B cells and DCs in healthy and infected monkeys suggests its possible use as a broad-acting adjuvant to be applied in the rhesus macaque model for the development of preventative and therapeutic vaccines.
authors.affiliation: Population Council, 1230 York Avenue, New York, NY 10021, USA.
authors.forename: N
authors.initials: N
authors.lastname: Teleshova
authors.forename: J
authors.initials: J
authors.lastname: Kenney
authors.forename: V
authors.initials: V
authors.lastname: Williams
authors.forename: G
authors.initials: G
authors.lastname: Van Nest
authors.forename: J
authors.initials: J
authors.lastname: Marshall
authors.forename: J D
authors.initials: JD
authors.lastname: Lifson
authors.forename: I
authors.initials: I
authors.lastname: Sivin
authors.forename: J
authors.initials: J
authors.lastname: Dufour
authors.forename: R
authors.initials: R
authors.lastname: Bohm
authors.forename: A
authors.initials: A
authors.lastname: Gettie
authors.forename: M
authors.initials: M
authors.lastname: Pope
mesh_terms: D016915:AIDS Vaccines / Q000494:pharmacology*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D023201:CD40 Ligand / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000276:immunology; D002908:Chronic Disease; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D066298:In Vitro Techniques; D008253:Macaca mulatta; D008297:Male; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D009841:Oligonucleotides / Q000494:pharmacology*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; C474878:C274 oligonucleotide; C408982:CPG-oligonucleotide; D018925:Chemokines; D016207:Cytokines; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; D023201:CD40 Ligand; C489630:1018 oligonucleotide