In-Clinic Latanoprost As a Novel Vaccine Adjuvant

拉坦前列素作为一种新型疫苗佐剂 摘要 为新型、有效和转译疫苗发现具有有效佐剂特性的临床化合物 是一个高度优先的研究领域。通过对美国国立卫生研究院临床资料的筛选，确定了住院患者 药物拉坦前列素在皮肤中触发促炎介质的表达，增加皮肤的渗透 树突状细胞(DC)亚群及增强诱导抗原特异性干扰素γ+CD8T细胞的保护作用 免疫微针阵列皮肤接种。在皮内和肌肉接种中， 拉坦前列素促进抗原特异性抗体，包括有效的抗病原体免疫球蛋白亚类。我们 假设拉坦前列素作为一种新型T细胞和抗体促进佐剂用于增强疫苗 疗效有两个目的：1)通过DC亚群确定拉坦前列素疫苗的佐剂效果；2)评价拉坦前列素疫苗的佐剂效果 拉坦前列素对皮肤和肌肉注射疫苗的佐剂作用。如果成功，我们的发现 拉坦前列素作为一种新型、安全、有效的皮肤和肌肉内T细胞和抗体促进佐剂 疫苗接种对这种临床药物在免疫接种中的再利用具有临床意义。

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.