378 Hydroxypropyl beta cyclodextrin barrier prevents respiratory and eye viral infections

I. Asante, Angela Lu, M. Humayun, Stan Louie
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Abstract

OBJECTIVES/GOALS: Susceptible mucocutaneous membranes of the eye and nasal cavity are easily infected by viruses leading to pink eye or respiratory infections whose direct cost has been estimated as $16 billion annually in the United States. We have developed a novel and effective barrier that will be agnostic to variants enveloped viruses like coronaviruses. METHODS/STUDY POPULATION: We evaluated the efficacy of hydroxypropyl cyclodextrin barrier in preventing respiratory coronavirus infections using 25 humanized angiotensin converting enzyme-2 receptor (hACE-2) mice under a BSL3 laboratory setting. We have shown the barrier is safe and efficacious in preventing coronavirus infections in in vitro respiratory cell lines. We instilled 10 uL aliquot of the barrier into the nostril of the mouse 30 minutes before exposing them to a 10uL titer containing 10,000 plaque forming units of the SARS-CoV-2 delta variant. The control mice received the SARS-CoV-2 infection but not the barrier. The mice were observed for 5 days after which they were sacrificed. We analyzed the lungs and nasal palates for viral load using reverse transcription-polymerase chain reaction. RESULTS/ANTICIPATED RESULTS: We observed our barrier to be effective in preventing SARS-CoV-2 delta variant infection in hACE2 mice models. The lungs and nasal secretions of treated mice were less infectious with lower viral load than the control mice. The lungs of treated mice showed decrease in IFN gene expression and many cytokines and chemokines that regulate virally induced inflammatory responses such as IL-1b, IL-8, CXCL9, CXCL10, and the CCLs. We observed the plasma Angiotensin I and Angiotensin II decreased with barrier treatment, correlating with the viral load observed in the lungs. These peptides may be useful biomarkers for monitoring viral load within the lungs of virally infected individuals. DISCUSSION/SIGNIFICANCE: This supports the barrier’s efficacy to reduce transmission and prevent infections of SARS-CoV-2. This easy to use barrier can augment the mucocutaneous layers of the eye and nasal cavity. Our agnostic barrier will reduce the economic and public health burden of seasonal respiratory and eye viral infections and their related deaths amongst the public.
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378 羟丙基 beta 环糊精屏障可预防呼吸道和眼部病毒感染
目的/目标:眼部和鼻腔的易感粘膜很容易受到病毒感染,导致红眼病或呼吸道感染,据估计,美国每年因此造成的直接损失高达 160 亿美元。我们已经开发出一种新型有效的屏障,它对冠状病毒等变异包膜病毒没有影响。方法/研究对象:我们在 BSL3 实验室环境下使用 25 只人源化血管紧张素转换酶-2 受体(hACE-2)小鼠评估了羟丙基环糊精屏障在预防呼吸道冠状病毒感染方面的功效。我们的研究表明,该屏障在体外呼吸细胞系中预防冠状病毒感染方面安全有效。我们在小鼠暴露于含有 10,000 个斑块形成单位的 10uL 滴度 SARS-CoV-2 delta 变体前 30 分钟,将 10 uL 等量的屏障注入小鼠鼻孔。对照组小鼠接受了 SARS-CoV-2 感染,但没有接受屏障感染。观察小鼠 5 天后将其处死。我们使用反转录聚合酶链反应分析了肺部和鼻腭部的病毒载量。结果/预期结果:我们观察到我们的屏障能有效预防 hACE2 小鼠模型感染 SARS-CoV-2 delta 变体。与对照组小鼠相比,经处理小鼠的肺部和鼻腔分泌物感染性较低,病毒载量也较低。治疗后小鼠肺部的 IFN 基因表达和许多调节病毒诱导的炎症反应的细胞因子和趋化因子(如 IL-1b、IL-8、CXCL9、CXCL10 和 CCLs)均有所减少。我们观察到,血浆血管紧张素 I 和血管紧张素 II 在屏障治疗后下降,这与肺部观察到的病毒载量相关。这些肽可能是监测病毒感染者肺部病毒负荷的有用生物标志物。讨论/意义:这支持了屏障在减少传播和预防 SARS-CoV-2 感染方面的功效。这种易于使用的屏障可增强眼部和鼻腔的粘膜层。我们的不可知屏障将减轻季节性呼吸道和眼部病毒感染的经济和公共卫生负担,并减少与之相关的公众死亡。
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