Safety and In Vivo Efficacy of Innate (Class R) and Broadly Reactive (Class B) Inhibitory Oligonucleotides (INH-ODN) in MRL-Fas/lpr Lupus Mice

Abstract

The vertebrate innate immune system uses pattern recognition receptors, including the Toll-like receptors (TLRs), specifically to detect pathogen-associated molecular patterns (PAMPs) present in infectious agents. Synthetic TLR ligands have also been identified, including imidazoquinoline compounds such as Imiquimod and Resiquimod (R-848), which activate human TLR7 and 8. Many of these ligands can modulate innate as well as adaptive immune responses and are evaluated as potential vaccine adjuvants. This chapter focuses on the TLR9 agonist CpG ODN as an immune adjuvant for infectious disease, cancer, and asthma/allergy. CpG ODN is demonstrated to be a well tolerated and effective adjuvant in numerous animal models and humans. These studies indicate that CpG ODN can stimulate strong Thl responses against a variety of antigens and demonstrate the potential of CpG ODN as an adjuvant in vaccines against infectious disease (both prophylactic and therapeutic), cancer, asthma, and allergy Clinical data obtained thus far are extremely encouraging, at least for prophylactic vaccines, and a number of trials are ongoing to further evaluate this technology, especially in therapeutic settings. For future development in humans, it may be desirable to further develop formulations to protect the antigen, improve uptake by immune cells, allow mucosal delivery, and possibly allow lower doses of antigen or fewer vaccine doses to be used.