CpG Motif Identification for Veterinary and Laboratory Species Demonstrates That Sequence Recognition Is Highly Conserved

Rankin, Robert; Pontarollo, Reno; Ioannou, Xenia P.; Krieg, Arthur Μ.; Hecker, Rolf; Babiuk, Lorne A.; Hurk, Sylvia van Drunen Littel‐van den

doi:10.1089/108729001753231713

Cited by 208 publications

(128 citation statements)

References 33 publications

Supporting

Mentioning

124

Contrasting

Order By: Relevance

“…Table V shows the immunostimulatory activity of some PyNTTT TGT ODNs on PBMC from different mammal species. As shown, these ODNs were active in animals within the order Primate, while ODN 2006 was active in all of them as previously reported (21). However, we observed a small, but reproducible, immunostimulatory activity (represented by Ϯ in Table V) on PBMC of nonprimate mammals using ODN IMT504, which possesses two CATTTTGT motifs.…”

Section: Odn 2006 Has Two Independent Immunostimulatory Motifssupporting

confidence: 86%

“…ODN 2006 has been found to be very active in several species of mammals (21). However, ODNs containing exclusively the PyNTTTTGT immunostimulatory motif described here are mainly active within the order Primate.…”

Section: Discussionmentioning

confidence: 66%

“…For example, the optimal CpG motif for mice has been reported to be GACGTT (2), and that for humans and other primates is GTCGTT (20). CpG-ODNs with phosphorotioate bonds including this last motif have been reported to be among the most active in sheep, goats, horses, pigs, dogs, cats, chickens, and cotton rats (21). This suggested a high degree of evolutionary conservation in recognition mechanisms for immunostimulatory ODNs.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Strong Cytosine-Guanosine-Independent Immunostimulation in Humans and Other Primates by Synthetic Oligodeoxynucleotides with PyNTTTTGT Motifs

Elı́as

Fló

López

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

Synthetic oligodeoxynucleotides (ODNs) containing cytosine-guanosine (CpG) motifs stimulate B and plasmacytoid dendritic cells of the vertebrate immune system. We found that in primates strong stimulation of these cells could also be achieved using certain non-CpG ODNs. The immunostimulatory motif in this case is a sequence with the general formula PyNTTTTGT in which Py is C or T, and N is A, T, C, or G. Assays performed on purified cells indicated that the immunostimulatory activity is direct. The use of a nuclease-resistant phosphorothioate backbone is not a necessary condition, since phosphodiester PyNTTTTGT ODNs are active. It was also demonstrated that ODN 2006, a widely used immunostimulant of human B cells, possess two kinds of immunostimulatory motifs: one of them mainly composed of two successive TCG trinucleotides located at the 5′ end and another one (duplicated) of the PyNTTTTGT kind here described. Even though PyNTTTTGT ODNs are mainly active on primate cells, some of them, bearing the CATTTTGT motif, have a small effect on cells from other mammals. This suggests that the immunostimulatory mechanism activated by these ODNs was present before, but optimized during, evolution of primates. Significant differences in the frequency of PyNTTTTGT sequences between bacterial and human DNA were not found. Thus, the possibility that PyNTTTTGT ODNs represent a class of pathogen-associated molecular pattern is unlikely. They could, more reasonably, be included within the category of danger signals of cell injury.

show abstract

Section: Odn 2006 Has Two Independent Immunostimulatory Motifssupporting

confidence: 86%

Section: Discussionmentioning

confidence: 66%

mentioning

confidence: 99%

See 1 more Smart Citation

Strong Cytosine-Guanosine-Independent Immunostimulation in Humans and Other Primates by Synthetic Oligodeoxynucleotides with PyNTTTTGT Motifs

Elı́as

Fló

López

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Primates appear to be much less sensitive to these effects. Most phosphorothioate oligodeoxynucleotides produce some immune stimulation in rodents, however oligonucleotides containing specific sequence motifs can exhibit profound immune stimulation (Krieg et al, 1995;Rankin et al, 2001). Immunostimulatory motifs include specific palindromic sequences and CpG (cytosine-guanosine) motifs (Rankin et al, 2001).…”

Section: Pharmacokinetics and Toxicity Of Oligonucleotidesmentioning

confidence: 99%

Antisense oligonucleotide-based therapeutics for cancer

2003

View full text Add to dashboard Cite

There has been steady progress in antisense technology over the past 14 years. We now have a far better appreciation of the attributes and limitations of the technology. Antisense oligonucleotides have been used to selectively inhibit thousands of genes in mammalian cells, hundreds, if not thousands, of genes in rodents and other species and multiple genes in humans. There are over 20 antisense drugs currently in clinical trials, several of which are showing promising results. Like any other class of drugs in development, there will continue to be successes and failures in the clinic. Despite some disappointments with the technology, it appears to be a valid platform for both drug discovery and as an experimental tool for functionalizing genes. Advances in the medicinal chemistry and formulation of antisense oligonucleotides will further enhance their therapeutic and commercial potential.

show abstract

“…The endotoxin level, determined using the QCL-1000 Chromogenic Limulus amoebocyte lysate test (BioWhittaker), was 51 ng NS3 protein mg 21 . ODN 1826 (59-CCATGACGTTCCTGACGTT-39) (Qiagen), which is a strong immune cell mitogen known to stimulate mouse splenocytes in vitro (Davis et al, 1998;Rankin et al, 2001), was used in this study. The CpG ODN was phosphorothioate modified to increase resistance to nuclease degradation (Samani et al, 2001).…”

mentioning

confidence: 99%

Dendritic cells pulsed with hepatitis C virus NS3 protein induce immune responses and protection from infection with recombinant vaccinia virus expressing NS3

Huang

Xiang

et al. 2006

Journal of General Virology

Self Cite

View full text Add to dashboard Cite

Infections with Hepatitis C virus (HCV) pose a serious health problem worldwide. In this study, the hypothesis that adoptive transfer of dendritic cells (DCs) pulsed with HCV NS3 protein and matured with an oligodeoxynucleotide (ODN) containing CpG motifs (CpG) ex vivo would initiate potent HCV-specific protective immune responses in vivo was tested. NS3 protein was efficiently transduced into DCs and treatment of DCs with CpG ODN induced phenotypic maturation and specifically increased the expression of CD40. DCs matured with CpG ODN produced higher interleukin 12 levels and a stronger allogeneic T-cell response compared with untreated DCs. Notably, there were no differences between NS3-pulsed DCs and DCs pulsed with a control protein with respect to phenotype, cytokine production or mixed lymphocyte reaction, indicating that transduction with NS3 protein did not impair DC functions. Compared with the untreated NS3-pulsed DCs, the NS3-pulsed DCs matured with CpG ODN induced stronger cellular immune responses including enhanced cytotoxicity, higher interferon-c production and stronger lymphocyte proliferation. Upon challenge with a recombinant vaccinia virus expressing NS3, all mice immunized with NS3-pulsed DCs showed a significant reduction in vaccinia virus titres when compared with mock-immunized mice. However, the NS3-pulsed DCs matured with CpG ODN induced higher levels of protection compared with the untreated NS3-pulsed DCs. These data are the first to show that NS3-pulsed DCs induce specific immune responses and provide protection from viral challenge, and also demonstrate that CpG ODNs, which have a proven safety profile, would be useful in the development of DC vaccines. INTRODUCTIONInfections with Hepatitis C virus (HCV) pose a serious health problem worldwide. An estimated 170 million people are currently infected, which amounts to 3 % of the world population. About 80 % of infected people remain chronic carriers and are at high risk of developing severe liver disease including cirrhosis and hepatocellular carcinoma (WHO, 1999). Treatment with interferon-a (IFN-a) and ribavirin is the only effective therapy against HCV infection, but the overall response rate is only 40-50 % (Fried et al., 2002;Manns et al., 2001). Currently, there is no licensed vaccine against HCV; therefore, developing strategies for vaccination as well as for treatment of HCV infection is of great importance.Dendritic cells (DCs) are the most potent type of antigen presenting cells (APCs) and are responsible for the initiation and maintenance of immune responses. Situated in peripheral tissues and in lymphoid organs, DCs are uniquely suited to detect and capture pathogens. They express members of the recently identified Toll-like receptor (TLR) family, which bind common chemical moieties associated with microbial organisms. TLR ligands include bacterial lipopolysaccharide, lipopeptides, hypomethylated CpG DNA motifs, dsRNA and flagellin (Akira et al., 2001;Iwasaki & Medzhitov, 2004). TLR signalling triggers a maturation program...

show abstract

CpG Motif Identification for Veterinary and Laboratory Species Demonstrates That Sequence Recognition Is Highly Conserved

Cited by 208 publications

References 33 publications

Strong Cytosine-Guanosine-Independent Immunostimulation in Humans and Other Primates by Synthetic Oligodeoxynucleotides with PyNTTTTGT Motifs

Strong Cytosine-Guanosine-Independent Immunostimulation in Humans and Other Primates by Synthetic Oligodeoxynucleotides with PyNTTTTGT Motifs

Antisense oligonucleotide-based therapeutics for cancer

Dendritic cells pulsed with hepatitis C virus NS3 protein induce immune responses and protection from infection with recombinant vaccinia virus expressing NS3

Contact Info

Product

Resources

About