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

靶向 IRF 的免疫佐剂增强西尼罗河病毒、登革热病毒、寨卡病毒和日本脑炎病毒疫苗的免疫原性

• 批准号: 9492480
• 负责人: JAY NELSON
• 金额: $ 251.34万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2018-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9492480
• 关键词: Adjuvant; Animal Model; Antiviral Agents; Cells; Computer Simulation; Contractor; Dendritic Cells; Dengue Virus; Dimerization; Emerging Communicable Diseases; Formulation; Human; IRF1 gene; IRF3 gene; Immunologic Adjuvants; Immunologic Factors; Interferons; Japanese encephalitis virus; Lead; Libraries; National Institute of Allergy and Infectious Disease; Pharmaceutical Chemistry; RNA Viruses; Research; Signal Pathway; Signaling Molecule; Structure-Activity Relationship; Study models; Testing; Therapeutic; Vaccine Adjuvant; Vaccines; Validation; West Nile virus; Work; Zika Virus; adaptive immune response; dimer; high throughput screening; human disease; immunogenicity; in vivo; novel; pathogen; programs; receptor; small molecule; small molecule libraries; vaccine candidate

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.

辅助发现计划支持疫苗新型辅助候选物的早期发现和初始表征。该研究必须包括（1）通过高吞吐量筛选（HTS）方法和验证，导致化合物刺激人类细胞的新佐剂候选者； （2）确定精选铅化合物的作用机理，包括鉴定受体辅助候选者的作用以及它们激活的细胞信号传导途径； （3）在结构活性关系（SAR）研究的指导下，通过制定和药物化学对铅候选者进行优化； （4）在动物模型中，铅化合物作为疫苗佐剂的疗效的验证。 项目必须包括动物模型研究，以测试辅助候选疫苗的反对： a）一个或多个niaid出现和重新出现感染病病原体 b）一种或多种尼亚德（Niaid）出现和重新出现的传染病病原体以及与人类疾病相关的一种或多种或多种（非HIV）病原体。