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Antiinfective Applications of Toll-like Receptor 9 Agonists

¹ Coley Pharmaceutical Group, Inc., Wellesley, Massachusetts

Correspondence and requests for reprints should be addressed to Arthur M. Krieg, M.D., Coley Pharmaceutical Group, Inc., 93 Worcester Street, Suite 101, Wellesley, MA 02481. E-mail: akrieg{at}coleypharma.com

ABSTRACT

The innate immune system detects pathogens by the presence of highly conserved pathogen-expressed molecules, which trigger host immune defenses. Toll-like receptor (TLR) 9 detects unmethylated CpG dinucleotides in bacterial or viral DNA, and can be stimulated for therapeutic applications with synthetic oligodeoxynucleotides containing immune stimulatory "CpG motifs." TLR9 activation induces both innate and adaptive immunity. The TLR9-induced innate immune activation can be applied in the prevention or treatment of infectious diseases, and the adaptive immune–enhancing effects can be harnessed for improving vaccines. This article highlights the current understanding of the mechanism of action of CpG oligodeoxynucleotides, and provides an overview of the preclinical data and early human clinical trial results, applying these TLR9 agonists in the field of infectious diseases.

Key Words: innate immunity • dendritic cell • infection • cytokine

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