Sterically stabilized cationic liposomes improve the uptake and immunostimulatory activity of CpG oligonucleotides

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2001-09-15

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Gursel, I
Gürsel, Mayda
Ishii, KJ
Klinman, DM

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Immunostimulatory CpG oligonucleotides (ODN) show promise as immune adjuvants, anti-allergens, and immunoprotective agents. Increasing the bioavailability and duration of action of CpG ODN should improve their therapeutic utility. Encapsulating ODN in sterically stabilized cationic liposomes provides protection from serum nucleases while facilitating uptake by B cells, dendritic cells, and macrophages. In a pathogen challenge model, sterically stabilized cationic liposomes encapsulation doubled the duration of CpG ODN-induced immune protection. In an immunization model, coencapsulation of CpG ODN with protein Ag (OVA) magnified the resultant Ag-specific IFN-gamma and IgG responses by 15- to 40-fold compared with Ag plus CpG ODN alone. These findings support the use of sterically stabilized cationic liposomes to significantly enhance the therapeutic efficacy of CpG ODN.

Subject Keywords

Immunology

URI

https://hdl.handle.net/11511/37248

Journal

JOURNAL OF IMMUNOLOGY

DOI

https://doi.org/10.4049/jimmunol.167.6.3324

Collections

Department of Biology, Article

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Repetitive elements in mammalian telomeres suppress bacterial DNA-induced immune activation. Gursel, I; Gürsel, Mayda; Yamada, H; Ishii, KJ; Takeshita, F; Klinman, DM (The American Association of Immunologists, 2003-08-01) Bacterial DNA contains immunostimulatory CpG motifs that trigger an innate immune response capable of promoting host survival following infectious challenge. Yet CpG-driven immune activation may also have deleterious consequences, ranging from autoimmune disease to death. We find that repetitive elements present at high frequency in mammalian telomeres, but rare in bacteria, down-regulate CpG-induced immune activation. Suppressive activity correlates with the ability of telomeric TTAGGG repeats to form G-te...
CpG RNA: identification of novel single-stranded RNA that stimulates human CD14+CD11c+ monocytes. Sugiyama, T; Gürsel, Mayda; Takeshita, F; Coban, C; Conover, J; Kaisho, T; Akira, S; Klinman, DM; Ishii, KJ (The American Association of Immunologists, 2005-02-15) Synthetic immunostimulatory nucleic acids such as CpG DNA are being harnessed therapeutically as vaccine adjuvants, anticancer or antiallergic agents. Efforts to identify nucleic acid-based agents capable of more specifically modulating the immune system are being developed. The current study identifies a novel class of single-stranded oligoribonucleotides (ORN) containing unmethylated CpG motifs and a poly(G) run at the 3 end (CpG ORN) that directly stimulate human CD14 CD11c monocytes but not dendritic ...
CpG oligodeoxynucleotides protect normal and SIV-infected macaques from Leishmania infection. Verthelyi, D; Gürsel, Mayda; Kenney, RT; Lifson, JD; Liu, S; Mican, J; Klinman, DM (The American Association of Immunologists, 2003-05-01) Oligodeoxynucleotides containing CpG motifs (CpG ODNs) mimic microbial DNA and activate effectors of the innate immune response, which limits the spread of pathogens and promotes an adaptive immune response. CpG ODNs have been shown to protect mice from infection with intracellular pathogens. Unfortunately, CpG motifs that optimally stimulate humans are only weakly active in mice, mandating the use of nonhuman primates to monitor the activity and safety of "human" CpG ODNs in vivo. This study demonstrates t...
Human peripheral blood cells differentially recognize and respond to two distinct CpG motifs Verthelyi, D; Ishii, KJ; Gürsel, Mayda; Takeshita, F; Klinman, DM (The American Association of Immunologists, 2001-02-15) Oligodeoxynucleotides (ODN) that contain unmethylated CpG dinucleotides trigger a strong innate immune response in vertebrates. CpG ODN show promise as vaccine adjuvants, anti-allergens, and immunoprotective agents in animal models. Their transition to clinical use requires the identification of motifs that are optimally stimulatory in humans. Analysis of hundreds of novel ODN resulted in the identification and characterization of two structurally distinct "clusters" of immunostimulatory CpG ODN, One cluste...
Differential and competitive activation of human immune cells by distinct classes of CpG oligodeoxynucleotide Gürsel, Mayda; Gursel, I; Ishii, KJ; Klinman, DM (2002-05-01) Synthetic oligodeoxynucleotides (ODN) expressing "CpG motifs" show promise as immune adjuvants, antiallergens, anticancer, and immuno-protective agents. Two structurally distinct classes of CpG ODN have been identified that stimulate human PBMC. This work establishes that both types of ODN bind to and are internalized by the same individual B cells, NK cells, and monocytes. However, the intracellular localization of "D" and "K" ODN differs, as does their functional activity: "K" type ODN trigger monocytes a...

Citation Formats

I. Gursel, M. Gürsel, K. Ishii, and D. Klinman, “Sterically stabilized cationic liposomes improve the uptake and immunostimulatory activity of CpG oligonucleotides,” JOURNAL OF IMMUNOLOGY, pp. 3324–3328, 2001, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/37248.