Innate Immune Adjuvant Discovery

The RIG-I-Like Receptors and Novel Innate Immune Pathways for Adjuvant Discovery and Development Program is focused on discovering and developing small molecule innate immune adjuvants that target either RIG-I-like receptors (RLRs) and pathways or novel innate immune factors and pathways, with the ultimate goal of enhancing immunity against RNA virus infection. RLRs are a family of cellular RNA helicases that function as innate immune receptors for specific RNA virus ligands. When activated, RLRs stimulate innate and adaptive immune responses. By targeting RLRs and their pathways, our goal is to discover and develop adjuvants that override virus countermeasures of RLR signaling; thus serving to stimulate, restore, and enhance innate antiviral immunity against pathogenic RNA viruses. Importantly, these compounds are also likely to display antiviral properties that are independent of an immunogen or vaccination strategy.

Four Research Areas:

The collaboration structure is designed to emphasize research strengths from the Gale Laboratory at the University of Washington and Kineta Inc.

• High-Throughput screening:   High-throughput screening of small-molecule compound libraries to identify RLR adjuvants and novel cellular factors and pathways that induce innate immunity and immune enhancement.
• Mechanisms of action:  Cell-based biochemical and functional genomics studies to assess the mechanisms of innate immune action of adjuvant compounds and factors identified through high-throughput screening.
• Lead compound optimization:  Lead compound optimization and iterative testing using in vitro and in vivo models linked to biochemical analyses and functional genomic and pathway modeling studies.
• Preclinical testing:  Preclinical testing of lead compounds in vitro and in vivo for adjuvant and antiviral actions against RNA viruses of public health importance, including hepatitis C, respiratory syncytial virus, influenza, and West Nile virus.