AUGMENTING THE QUALITY AND DURATION OF THE IMMUNE RESPONSE WITH A NOVEL TLR2 AGONIST-ALUMINUM COMBINATION ADJUVANT

使用新型 TLR2 激动剂-铝组合佐剂增强免疫反应的质量和持续时间

• 批准号: 10933287
• 负责人: KENTNER SINGLETON
• 金额: $ 30万
• 依托单位: TEICHOS LABORATORIES, LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2024-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10933287
• 关键词: Adjuvant; Affinity; Agonist; Aluminum; Aluminum Hydroxide; Amplifiers; Contractor; Diphtheria-Tetanus-acellular Pertussis Vaccines; Dose; Formulation; Immune response; Peptidoglycan; Performance; Phosphorylation; Production; Subunit Vaccines; TLR2 gene; Testing; Vaccine Adjuvant; Vaccines; aluminum sulfate; analog; immunogenicity; improved; novel; response

The project will optimize a novel adjuvant formulation composed of alum and TL-001, a unique totally synthetic peptidoglycan (sPGN) TLR2 agonist, to improve performance of a registered DTaP subunit vaccine. Preliminary results with TL-001 strongly suggest potential as a non-toxic, single agent vaccine adjuvant. TL-001 and a phosphonylated analogue (pTL-001) will be prepared and their respective affinities for aluminum hydroxide adjuvant (AH) will be compared. Proof-of-concept studies will determine if pTL-001, the novel, soluble, immune response amplifier, combined with alum, enhances the magnitude and quality of humoral and cellular responses compared to the registered vaccine. The project will scale production of TL-001 and pTL-001 for characterization of dose-related induction.

该项目将优化一种由明矾和TL-001组成的新型佐剂配方，TL-001是一种独特的全合成肽聚糖(SPGN)TLR2激动剂，以提高注册的DTaP亚单位疫苗的性能。TL-001的初步结果强烈表明，它有可能成为一种无毒的单剂疫苗佐剂。将制备TL-001和一种膦酰化类似物(PTL-001)，并比较它们对氢氧化铝佐剂(AH)的亲和力。概念验证研究将确定PTL-001，一种新型的，可溶的，免疫反应放大器，与明矾相结合，是否与注册疫苗相比，提高体液和细胞反应的幅度和质量。该项目将规模化生产TL-001和PTL-001，以表征与剂量相关的诱导。