Local and systemic effects of intranodally injected CpG-C immunostimulatory-oligodeoxyribonucleotides in macaques
Teleshova,Natalia; Kenney,Jessica; Van Nest,Gary; Marshall,Jason; Lifson,Jeffrey D.; Sivin,Irving; Dufour,Jason; Bohm,Rudolf; Gettie,Agegnehu; Robbiani,Melissa
Journal of Immunology 177(12): 8531-8541
Publication date: 2006
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 macaqueblood dendritic cells (DCs) and B cells and augments SIV-specificIFN- responses in vitro. To further explore the potential ofC274 for future vaccine studies, we assessed the in vivo effectsof locally administered C274 (in naive and healthy infectedmacaques). Costimulatory molecules were marginally increasedon DCs and B cells within cells isolated from C274-injectedlymph nodes (LNs). However, cells from C274-injected LNs exhibitedheightened responsiveness to in vitro culture. This was particularlyapparent at the level of CD80 (less so CD86) expression by CD123plasmacytoid DCs and was further boosted in the presence ofadditional C274 in vitro. Notably, cells from C274-injectedLNs secreted significantly elevated levels of several cytokinesand chemokines upon in vitro culture. This was more pronouncedwhen cells were exposed to additional stimuli in vitro, producingIFN-, IL-3, IL-6, IL-12, TNF-, CCL2, CCL3, CCL5, and CXCL8.Following C274 administration in the absence of additional SIVAg, endogenous IFN- secretion was elevated in LN cells of infectedanimals, but SIV-specific responses were unchanged. Endogenousand SIV-specific responses decreased in blood, before the SIV-specificresponses rebounded by 2 wk after C274 treatment. Elevated IFN-,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 immunefunction to enhance anti-HIV vaccine immunogenicity.