CpG Oligodeoxynucleotides as Vaccine Adjuvants in Primates

Verthelyi, Daniela; Kenney, Richard T.; Seder, Robert A.; Gam, Albert A.; Friedag, Brenda; Klinman, Dennis M.

doi:10.4049/jimmunol.168.4.1659

Cited by 174 publications

(153 citation statements)

References 38 publications

Supporting

Mentioning

143

Contrasting

Order By: Relevance

“…A similar time course was observed for the induction of immunoprotection by CpG ODNs in mice (18)(19)(20)28,29): protection generally developed several days after administration and persisted for 1-2 weeks (depending upon the pathogen). A longer delay is typical for the development of reactive arthritis in humans following bacterial infection (2,3).…”

Section: Discussionsupporting

confidence: 60%

Influence of stimulatory and suppressive DNA motifs on host susceptibility to inflammatory arthritis

Zeuner

Verthelyi

Gürsel

et al. 2003

Arthritis & Rheumatism

Self Cite

View full text Add to dashboard Cite

Objective. To examine whether systemic administration of immunostimulatory and immunosuppressive oligodeoxynucleotides (ODNs) alter host susceptibility to inflammatory arthritis.Methods. Normal BALB/c mice were treated systemically with CpG ODNs or suppressive ODNs, and then challenged intraarticularly with CpG DNA. The onset and magnitude of the resulting inflammatory response was monitored.Results. Systemic delivery of CpG ODNs significantly increased susceptibility to local inflammation, whereas systemic treatment with suppressive ODNs reduced this susceptibility. CD11c؉ cells played a key role in mediating host sensitivity to arthritis. These cells were the dominant source of tumor necrosis factor ␣ production in CpG-stimulated animals and transferred resistance to arthritis from mice treated with suppressive ODNs.Conclusion. Systemic exposure to immunostimulatory and immunosuppressive DNA influences host susceptibility to local inflammatory challenge. Current findings raise the possibility that suppressive ODNs may be useful in the prevention/treatment of proinflammatory diseases.

show abstract

Section: Discussionsupporting

confidence: 60%

Influence of stimulatory and suppressive DNA motifs on host susceptibility to inflammatory arthritis

Zeuner

Verthelyi

Gürsel

et al. 2003

Arthritis & Rheumatism

Self Cite

View full text Add to dashboard Cite

show abstract

“…This report documents that bioactive CpG motifs induce dose-dependent neovascularization in the corneas of mice engrafted with hydron pellets containing CpG ODN or HSV DNA. These results were obtained by using a mixture of two ODN that expressed different CpG motifs, because such combinations are more broadly stimulatory than individual ODN and are more representative of the multiple motifs found in HSV DNA (24).…”

Section: Discussionmentioning

confidence: 99%

DNA containing CpG motifs induces angiogenesis

Zheng

Klinman

Gieryńska

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

New blood vessel formation in the cornea is an essential step in the pathogenesis of a blinding immunoinflammatory reaction caused by ocular infection with herpes simplex virus (HSV). By using a murine corneal micropocket assay, we found that HSV DNA (which contains a significant excess of potentially bioactive ''CpG'' motifs when compared with mammalian DNA) induces angiogenesis. Moreover, synthetic oligodeoxynucleotides containing CpG motifs attract inflammatory cells and stimulate the release of vascular endothelial growth factor (VEGF), which in turn triggers new blood vessel formation. In vitro, CpG DNA induces the J774A.1 murine macrophage cell line to produce VEGF. In vivo CpG-induced angiogenesis was blocked by the administration of anti-mVEGF Ab or the inclusion of ''neutralizing'' oligodeoxynucleotides that specifically oppose the stimulatory activity of CpG DNA. These findings establish that DNA containing bioactive CpG motifs induces angiogenesis, and suggest that CpG motifs in HSV DNA may contribute to the blinding lesions of stromal keratitis.pathogenesis ͉ HSV ͉ VEGF

show abstract

“…The role of immune modulation of unmethylated CpG in governing the immune response has been described both in rodents and in nonhuman primates. 48,49 Thus, as a number of CpG has been introduced into the synthetic cDNA of CEA, these may also contribute to the enhanced immunogenic properties of the CEA expressing vectors.…”

Section: Discussionmentioning

confidence: 99%

Efficient induction of T‐cell responses to carcinoembryonic antigen by a heterologous prime‐boost regimen using DNA and adenovirus vectors carrying a codon usage optimized cDNA

Mennuni

Calvaruso

Facciabene

et al. 2005

Intl Journal of Cancer

View full text Add to dashboard Cite

The immunogenic properties of plasmid DNA and recombinant adenovirus (Ad) encoding the carcinoembryonic antigen (CEA) were examined in mice by measuring both the amplitude and type of immune response, and the immunogenicity of codon usage optimized cDNA encoding CEA (CEAopt) was assessed both in C57Bl/6 and CEA transgenic mice. Vectors were injected into quadriceps muscle either alone or in combination, and plasmid DNA was electroporated to enhance gene expression efficiency and immunogenicity. Injection of plasmid pVIJ/CEA followed by Ad-CEA boost elicited the highest amplitude of both CD4 1 and CD8 1 T-cell response to the target antigen, measured by both IFNc-ELIspot assay and intracellular staining. Vectors carrying cDNA of CEAopt expressed a greater amount of the CEA protein than their wild-type counterparts, and this enhanced expression was associated with greater immunogenicity. Both CD4 1 and CD8 1 T-cell epitopes were mapped in the C-terminal portion of the protein. In CEA transgenic mice, only immunization based on repeated injections of pVIJ/ CEAopt followed by Ad-CEAopt was able to elicit a CEA-specific CD8 1 T-cell response, whereas the wild-type vectors did not break tolerance to this target antigen. MC38-CEA tumor cells injected s.c. in CEA transgenic mice vaccinated with CEAopt vectors exhibited delayed growth kinetics. These studies demonstrate that this type of genetic vaccine is highly immunogenic and can break tolerance to CEA tumor antigen in CEA transgenic mice. ' 2005 Wiley-Liss, Inc.Key words: CEA; DNA electroporation; adenovirus Despite improvements in prevention, early detection and treatment, the possibility of curing many cancer patients remains elusive. Thus, cancer continues to be a largely unmet medical need for which more efficient therapeutic strategies must be developed. 1 Particular attention has been given to active specific immunotherapy of cancer, whereby patients are immunized against antigens presented by tumor cells. In fact, experimental and clinical evidence have demonstrated the critical role played by the cellular and humoral responses in controlling tumor growth and metastasis. 2 Many of these therapies are specifically targeted to tumorassociated antigens among which carcinoembryonic antigen (CEA) is a frequent example due to its ectopic and deregulated expression in a large percentage of adenocarcinomas. 3 Human CEA is the prototypic member of the human CEA family, a group of highly glycosylated homotypic/heterotypic cell surface intracellular adhesion molecules, and part of the immunoglobulin gene superfamily. CEA is widely used as human tumor marker, is expressed mostly in the gastrointestinal tract and is overexpressed in many human cancers, including epithelial tumors originating from the gastrointestinal tract, lung, thyroid, breast, prostate, cervix and ovaries. 4 CEA has been the focus of extensive preclinical and clinical investigation aimed at developing a CEA-specific vaccine with a therapeutic impact on tumor progression. 5 In this context, genetic vacc...

show abstract

CpG Oligodeoxynucleotides as Vaccine Adjuvants in Primates

Cited by 174 publications

References 38 publications

Influence of stimulatory and suppressive DNA motifs on host susceptibility to inflammatory arthritis

Influence of stimulatory and suppressive DNA motifs on host susceptibility to inflammatory arthritis

DNA containing CpG motifs induces angiogenesis

Efficient induction of T‐cell responses to carcinoembryonic antigen by a heterologous prime‐boost regimen using DNA and adenovirus vectors carrying a codon usage optimized cDNA

Contact Info

Product

Resources

About