In-Clinic Latanoprost As a Novel Vaccine Adjuvant

拉坦前列素作为新型疫苗佐剂的临床研究 摘要 发现用于新型、有效和转化疫苗的具有强效佐剂特性的临床化合物 是一个高度优先的研究领域。通过筛选NIH临床收集，我们已经确定了临床 药物拉坦前列素触发皮肤中促炎介质的表达，增加皮肤浸润， 树突状细胞（DC）亚群，并增强抗原特异性IFNγ+CD8 T细胞的诱导和保护性 微针阵列皮肤疫苗接种的免疫力。在皮内和肌内接种中， 拉坦前列素促进抗原特异性抗体（Ab），包括有效的抗病原体IgG亚类。我们 假设拉坦前列素作为一种新型T细胞和Ab促进佐剂， 有两个目的功效：1）通过DC亚群确定拉坦前列素的疫苗佐剂效应，2）评价 拉坦前列素对皮肤和肌肉接种的佐剂作用。如果成功的话， 拉坦前列素作为一种新型、安全、有效的皮肤和肌内免疫佐剂， 疫苗接种对于在免疫接种中重新利用这种临床药物具有临床意义。

In-Clinic Latanoprost As a Novel Vaccine Adjuvant Abstract Discovering in-clinic compounds with potent adjuvant properties for novel, effective and translational vaccines is a high-priority research area. Through screening the NIH Clinical Collection, we have identified the in-clinic drug Latanoprost triggering expression of proinflammatory mediators in skin, increasing skin-infiltration of dendritic cell (DC) subsets, and enhancing induction of antigen-specific IFNγ+CD8 T cells and protective immunity to the microneedle array cutaneous vaccination. In intradermal and intramuscular vaccinations, Latanoprost promotes antigen-specific antibodies (Ab), including the effective anti-pathogen IgG subclass. We hypothesize that Latanoprost functions as a novel T cell- and Ab-promoting adjuvant to enhance vaccine efficacy with two aims: 1) determine Latanoprost’s vaccine adjuvant effects via DC subsets, 2) evaluate Latanoprost’s adjuvant effects to skin and intramuscular vaccinations. If successful, our discovery of Latanoprost as a new, safe, and effective T cell- and Ab-promoting adjuvant to skin and intramuscular vaccinations would have a clinical significance on repurposing this in-clinic drug in immunizations.