| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Center for Biomedical Research, Population Council, New York, NY 10021;
Dynavax Technologies, Berkeley, CA 94710;
AIDS Vaccine Program, Science Applications International Corporation, National Cancer Institute, Frederick, MD 21702;
Tulane National Primate Research Center, Tulane University, Covington, LA 70433; and
¶ Aaron Diamond AIDS Research Center, New York, NY 10016
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-
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-
, IL-3, IL-6, IL-12, TNF-, CCL2, CCL3, CCL5, and CXCL8. Following C274 administration in the absence of additional SIV Ag, endogenous IFN- 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-, 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants R21 AI060405 and R01s AI040877 and DE016256 (to M.R.), as well as by funds from the Elizabeth Glaser Pediatric AIDS Foundation, and the Tulane National Primate Research Center National Institutes of Health Base Grant RR00164. M.R. is an Elizabeth Glaser Scientist. This work was also funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract NO1-CO-12400.
2 Current address: Division of Infectious Diseases, Mt. Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029.
3 Address correspondence and reprint requests to Dr. Melissa Robbiani, Center for Biomedical Research, Population Council, 1230 York Avenue, New York, NY 10021. E-mail address: mrobbiani{at}popcouncil.org
4 Abbreviations used in this paper: DC, dendritic cell; LN, lymph node; MDC, myeloid DC; PDC, plasmacytoid DC; ISS-ODN, immunostimulatory CpG-C oligodeoxyribonucleotide; SHIV, simian HIV; LNC, LN cell; MFI, mean fluorescence intensity; AT-2, aldrithiol-2; MV, microvesicle; SFC, spot-forming cell.
This article has been cited by other articles:
|
|
 |
|
  R. K. Reeves and P. N. Fultz Characterization of Plasmacytoid Dendritic Cells in Bone Marrow of Pig-Tailed Macaques Clin. Vaccine Immunol., January 1, 2008; 15(1): 35 - 41. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
