Poly-ICLC Prophylaxis Treatment of Ebola Virus Infection

在埃博拉病毒自然或故意暴发期间，暴露期预防是保护高危暴露目标人群的一种潜在有效方法。本提案中提出的临床前小鼠数据表明，poly-ICLC可以在疫情控制情况下提供这种保护，并且具有很高的安全边际。Poly-ICLC （Hiltonol(TM)）是一种稳定的、临床安全的、有效的、相对简单的dsRNA病毒模拟物，其广泛激活先天和适应性宿主免疫反应，在刺激长期特异性体液和细胞免疫的背景下，产生立即的非特异性抗病毒状态。经证实，无论是肌肉注射还是鼻内注射，它都具有广泛的抗病毒保护作用，这使其成为国家生物防御装备中潜在的有价值的制剂。

Peri-exposure prophylaxis is a potentially effective method of protecting targeted populations at high risk of exposure during a natural or intentional outbreak of Ebola virus. Preclinical murine data presented in this proposal indicates that poly-ICLC could provide such protection with a high safety margin in an epidemic containment situation. Poly-ICLC (Hiltonol(TM)) is a stabilized, clinically safe and active, yet relatively simple dsRNA viral-mimic whose broad activation of both innate and adaptive host immune responses results in an immediate non-specific antiviral state in the context of stimulation of longer-term specific humoral and cellular immunity. Its demonstrated broad antiviral protection when delivered either intramuscularly or intranasally make it a potentially valuable agent for inclusion in the Nation's biodefense armamentarium. General Aims: To accelerate the development of the dsRNA viral-mimic poly-ICLC (Hiltonol(TM)) as a safe, effective and logistically simple prophylaxis and early treatment for ebola virus infection in humans. Specific Aims: A) To determine the optimal dose and schedule of poly-ICLC for prophylaxis and treatment of Ebola virus infection in an established murine challenge model, and to further elucidate its mechanism of action and effect on viral load and on elements of innate and adaptive immunity B) To confirm the safety and efficacy of poly-ICLC in prophylaxis and treatment of ebola virus infection in a well-established non-human primate (cynomolgous) challenge model, utilizing the optimal dose schedules determined in the murine studies. C) To develop GMP manufacturing methods for Poly-ICLC, in compliance with specific FDA guidance.