Targeting IRFs for Immune Adjuvant Enhancement of Vaccine Immunogenicity in West Nile Virus, Dengue Virus, and Japanese Encephalitis Virus vaccines

佐剂发现项目支持新佐剂候选疫苗的早期发现和初步表征。研究必须包括：(1)通过高通量筛选（HTS）方法鉴定新的佐剂候选物，并验证先导化合物刺激人体细胞；(2)确定选定的先导化合物的作用机制，包括确定佐剂候选物通过的受体及其激活的细胞信号通路；(3)在构效关系（SAR）研究的指导下，通过配方和药物化学对候选先导药物进行优化；(4)在动物模型中验证铅化合物作为疫苗佐剂的有效性。

The Adjuvant Discovery Program supports the early stage discovery and initial characterization of novel adjuvant candidates for vaccines. The research must include (1) identification of novel adjuvant candidates through high throughput screening (HTS) approaches and validation that lead compounds stimulate human cells; (2) determination of the mechanism of action of select lead compounds, including the identification of the receptor(s) the adjuvant candidates work through and the cellular signaling pathways they activate; (3) optimization of lead candidates through formulation and medicinal chemistry, guided by structure-activity relationship (SAR) studies; and (4) verification of the efficacy of lead compounds as vaccines adjuvants in vivo in an animal model. Projects must include animal model studies to test the adjuvant candidates with vaccines against: A) One or more NIAID Emerging and Re-emerging Infectious Disease Pathogens http://www.niaid.nih.gov/topics/emerging/pages/default.aspx), or B) One or more NIAID Emerging and Re-emerging Infectious Disease Pathogens as well as one or more other (non-HIV) pathogens relevant to human disease.