title: Local and systemic effects of intranodally injected CpG-C immunostimulatory-oligodeoxyribonucleotides in macaques.
abstract: Immunostimulatory CpG-C oligodeoxyribonucleotides (ISS-ODNs) represent a promising strategy to enhance vaccine efficacy. We have shown that the CpG-C ISS-ODN C274 stimulates macaque blood dendritic cells (DCs) and B cells and augments SIV-specific IFN-gamma responses in vitro. To further explore the potential of C274 for future vaccine studies, we assessed the in vivo effects of locally administered C274 (in naive and healthy infected macaques). Costimulatory molecules were marginally increased on DCs and B cells within cells isolated from C274-injected lymph nodes (LNs). However, cells from C274-injected LNs exhibited heightened responsiveness to in vitro culture. This was particularly apparent at the level of CD80 (less so CD86) expression by CD123(+) plasmacytoid DCs and was further boosted in the presence of additional C274 in vitro. Notably, cells from C274-injected LNs secreted significantly elevated levels of several cytokines and chemokines upon in vitro culture. This was more pronounced when cells were exposed to additional stimuli in vitro, producing IFN-alpha, IL-3, IL-6, IL-12, TNF-alpha, CCL2, CCL3, CCL5, and CXCL8. Following C274 administration in the absence of additional SIV Ag, endogenous IFN-gamma secretion was elevated in LN cells of infected animals, but SIV-specific responses were unchanged. Endogenous and SIV-specific responses decreased in blood, before the SIV-specific responses rebounded by 2 wk after C274 treatment. Elevated IFN-alpha, CCL2, and CCL5 were also detected in the plasma after C274 injection. Thus, locally administered C274 has local and systemic activities, supporting the potential for CpG-C ISS-ODNs to boost immune function to enhance anti-HIV vaccine immunogenicity.
authors.affiliation: Center for Biomedical Research, Population Council, 1230 York Avenue, New York, NY 10021, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Teleshova
authors.forename: Jessica
authors.initials: J
authors.lastname: Kenney
authors.forename: Gary
authors.initials: G
authors.lastname: Van Nest
authors.forename: Jason
authors.initials: J
authors.lastname: Marshall
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Irving
authors.initials: I
authors.lastname: Sivin
authors.forename: Jason
authors.initials: J
authors.lastname: Dufour
authors.forename: Rudolf
authors.initials: R
authors.lastname: Bohm
authors.forename: Agegnehu
authors.initials: A
authors.lastname: Gettie
authors.forename: Melissa
authors.initials: M
authors.lastname: Robbiani
mesh_terms: D000818:Animals; D001402:B-Lymphocytes; D002478:Cells, Cultured; D016207:Cytokines; D003713:Dendritic Cells; D005260:Female; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology; D008251:Macaca; D008297:Male; D009841:Oligonucleotides / Q000008:administration & dosage / Q000494:pharmacology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000628:therapy; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects; D014612:Vaccines / Q000276:immunology*
chemical_list: C474878:C274 oligonucleotide; D016207:Cytokines; D007155:Immunologic Factors; D009841:Oligonucleotides; D014612:Vaccines