Format

Send to

Choose Destination
DNA Cell Biol. 2005 Feb;24(2):63-72.

Superior activity of the type C class of ISS in vitro and in vivo across multiple species.

Author information

1
Dynavax Technologies Corporation, Berkeley, California 94710, USA. jmarshall@dvax.com

Abstract

CpG-C are a novel class of CpG motif-containing immunostimulatory sequences (ISS) that includes both a 5'-TCG element and a CpG-containing palindrome. CpG-C drive all known ISS activities and, in particular, are potent enhancers of IFN-alpha from plasmacytoid dendritic cells (PDCs). In our examination of CpG-C sequence requirements, we determined that optimal IFN-alpha-inducing activity could be achieved with longer palindromes. Longer palindromes also correlated with maintenance of the double-stranded (ds) form despite concentration and pH changes, indicating a preference for ds oligodeoxynucleotides (ODNs) by the ISS-induced signaling mechanism for IFN-alpha synthesis. This correlation did not hold for all arms of the ISS-induced immune response, since we did not observe increased B cell activity with the longer palindrome CpG-C ODNs. We further demonstrated that CpG-C retained activity in an in vitro primate system and induced the expression of several cytokines and IFN-alpha-inducible genes when CpG-C were administered in vivo to mice and primates. In conclusion, we have shown CpG-C to exert several types of immune functions across multiple species, and this novel class is thus an attractive candidate for ISS-based therapeutic strategies.

PMID:
15699627
DOI:
10.1089/dna.2005.24.63
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center