AI Article Synopsis
- Researchers developed 15 new immune modulatory oligonucleotides (IMOs) as TLR9 agonists with specific chemical modifications to enhance immune responses.
- In lab studies, altering the number of immunostimulatory motifs showed minimal effects on immune stimulation, while adding self-complementary sequences significantly boosted stimulation in dendritic and B cells.
- All IMOs successfully triggered cytokine production in mice right after administration, and some compounds were tested in rhesus macaques for their ability to induce cytokines like IFN-alpha and IP-10.
Article Abstract
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.
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| http://dx.doi.org/10.1016/j.cellimm.2010.03.005 | DOI Listing |
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