Synthesis and immunological activities of novel agonists of toll-like receptor 9
| Autor: | Weiwen Jiang, Sudhir Agrawal, Andrew J. Bett, Ireneusz Nowak, Thomas Wisniewski, Sheri Dubey, Zhenhua Sun, Mallikarjuna Putta, Melissa Precopio, Danilo R. Casimiro, Hao Wang, Dong Yu, Ekambar R. Kandimalla, Jimmy X. Tang, Mary Struthers |
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| Rok vydání: | 2010 |
| Předmět: |
endocrine system
medicine.medical_treatment Immunology Oligonucleotides Pyrimidinones Biology Lymphocyte Activation Cell Line Mice Immune system In vivo medicine Animals Humans B cell Cell Proliferation B-Lymphocytes T-helper 1 type immune response Cell growth Interferon-alpha TLR9 hemic and immune systems Dendritic Cells Macaca mulatta In vitro Cell biology Mice Inbred C57BL Thiazoles Cytokine medicine.anatomical_structure Toll-Like Receptor 9 Female |
| Zdroj: | Cellular Immunology. 263:105-113 |
| ISSN: | 0008-8749 |
| DOI: | 10.1016/j.cellimm.2010.03.005 |
| Popis: | Novel agonists of TLR9 with two 5'-ends and synthetic immune stimulatory motifs, referred to as immune modulatory oligonucleotides (IMOs) are potent agonists of TLR9. In the present study, we have designed and synthesized 15 novel IMOs by incorporating specific chemical modifications and studied their immune response profiles both in vitro and in vivo. Analysis of the immunostimulatory profiles of these IMOs in human and NHP cell-based assays suggest that changes in the number of synthetic immunostimulatory motifs gave only a subtle change in immune stimulation of pDCs as indicated by IFN-alpha production and pDC maturation while the addition of self-complementary sequences produced more dramatic changes in both pDC and B cell stimulation. All IMOs induced cytokine production in vivo immediately after administration in mice. Representative compounds were also compared for the ability to stimulate cytokine production in vivo (IFN-alpha and IP-10) in rhesus macaques after intra-muscular administration. |
| Databáze: | OpenAIRE |
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