IFN-tau treatment in mice infected with cowpox virus

IFN-tau 治疗感染牛痘病毒的小鼠

• 批准号: 6735965
• 负责人: Lorelie Villarete
• 金额: $ 11.04万
• 依托单位: PEPGEN CORPORATION
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2005-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6735965
• 关键词: HeLa cells; Poxviridae; animal genetic material tag; antiviral agents; bioterrorism /chemical warfare; data collection methodology /evaluation; drug screening /evaluation; enzyme activity; enzyme induction /repression; immunotherapy; interferons; laboratory mouse; leukocyte activation /transformation; ligase; natural killer cells; nonhuman therapy evaluation; oral administration; polymerase chain reaction; receptor binding; smallpox virus

DESCRIPTION (provided by investigator): This SBIR Phase I project will evaluate the effects of orally administered Interferon-tau (t) (INF-tau) on lethal cowpox virus infection in mice. The effect of treatment will be based on the reduction of viral titer in the lungs and prevention of death of the infected mice. Induction of 2', 5'-oligoadenylate synthetase (OAS) and induction of natural killer (NK) cell activity, will also be determined as these activities are thought to mediate the anti-viral effects of IFN-tau. In this proposed project, the potential utility of oral IFN-t will be tested in mice infected with lethal cowpox virus. Both prophylactic and therapeutic protocols will be evaluated. IFN-tau is orally bioactive. When administered orally, IFN-tau induces OAS in mice and humans (Pepgen's unpublished data). When compared with recombinant human IFN-alpha, both IFN-t and rhlFN-alpha could increase the sheep Natural Killer (NK) activity to kill human target cells at very low concentration. IFN-tau also demonstrated to be able to suppress viral replication of human papillomavirus, human immunodeficiency virus, human hepatitis B virus and feline immunodeficiency virus, and murine Theiler's virus. In addition to its convenience of oral intake, one of IFN-tau's advantages is its low side effect and low toxicity profile. In a bioterrorist scenario smallpox virus is expected to be transmitted by aerosol and the number of exposed individuals could be very large. Moreover, under such a scenario the population could face repeated and prolonged exposure to the virus. Therefore, it will be important not only to treat infected individuals in an effort to save their lives but also to curtail a potential epidemic by blocking new infections and secondary transmission. A drug which can provide both prophylactic and therapeutic benefit, with easy use (oral administration) and less toxic would be ideal.

描述（由研究人员提供）：该SBIR I期项目将评估口服施用的干扰素-TAU（T）（INF-TAU）对小鼠致命性牛pox病毒感染的影响。治疗的作用将基于肺中病毒滴度的减少和预防感染小鼠的死亡。还将确定2'，5'-橄榄二腺苷酸合成酶（OAS）和自然杀伤（NK）细胞活性的诱导，因为这些活性被认为可以介导IFN-TAU的抗病毒作用。在这个拟议的项目中，将在感染致命牛pox病毒的小鼠中测试口服IFN-T的潜在效用。预防性和治疗方案均可评估。 IFN-TAU是口服生物活性的。口服时，IFN-TAU会在小鼠和人类中诱导OA（Pepgen的未发表数据）。与重组人IFN-Alpha相比，IFN-T和RHLFN-Alpha都可以增加绵羊天然杀手（NK）活性，以极低的浓度杀死人类靶细胞。 IFN-TAU还证明能够抑制人乳头瘤病毒，人免疫缺陷病毒，人乙型肝炎病毒和猫免疫缺陷病毒以及鼠类Theiler病毒的病毒复制。除了方便口服摄入量外，IFN-Tau的优势之一是其低副作用和低毒性特征。 在生物恐怖主义的情况下，天花病毒预计将由气溶胶传播，暴露的个体的数量可能非常大。此外，在这种情况下，人口可能会面临反复和长时间接触该病毒的情况。因此，不仅要治疗受感染的人来挽救生命，而且要通过阻止新的感染和次要传播来削弱潜在的流行病，这将非常重要。可以提供预防性和治疗益处的药物，易于使用（口服给药），而毒性较少是理想的。