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

该项目将优化一种由明矾和TL-001（一种独特的全合成肽聚糖（sPGN） TLR2激动剂）组成的新型佐剂配方，以提高已注册的DTaP亚单位疫苗的性能。初步结果表明，TL-001可能是一种无毒的单剂疫苗佐剂。将制备TL-001和一种膦化类似物（pTL-001），并比较它们对氢氧化铝佐剂（AH）的亲和度。概念验证研究将确定，与已注册疫苗相比，新型可溶性免疫反应放大器pTL-001与明矾结合后，是否能提高体液和细胞反应的强度和质量。该项目将扩大TL-001和pTL-001的生产规模，用于剂量相关诱导的表征。

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.