IMMUNOTHERAPY OF VIRAL PNEUMONIAS OF INFANTS

病毒性细支气管炎和肺炎是发病的主要原因， 婴儿和儿童的死亡率，通常由呼吸道疾病引起。 合胞病毒（RSV）或副流感病毒3型（PIV3），其可以是 每年造成10亿美元的医疗费用和1万人死亡 在美国这两种病毒都没有获得许可的疫苗， 唯一获得许可的药物利巴韦林（Ribavirin TM）效力有限。同相 I活动，我们表明，局部抗体引起病毒清除 而不减少损伤。曲安奈德单独清除 肺部病变，但导致病毒增加10倍， 一起消毒了肺部并逆转了病变。在第二阶段的工作中， 我们将测试四种糖皮质激素， 全身活动减少。然后我们将研究潜在的广度 通过用已建立的RSV治疗棉鼠， （包膜，RNA）和5型腺病毒（无包膜，DNA）病毒 肺炎糖皮质激素在逆转人乳腺癌中的作用机制 病毒性肺炎的损伤将在小鼠模型中评估， 腺病毒肺炎我们预计将启动临床试验 第二阶段工作范围完成后立即进行。 拟议的商业应用：目前尚无有效的治疗方法 确诊的病毒性细支气管炎和肺炎局部治疗， 抗病毒抗体和糖皮质激素的组合显示， 在第一阶段工作中有效和安全，我们将把它扩展到两个 II期的其他病毒性肺炎。

Viral bronchiolitis and pneumonia are major causes of morbidity and mortality in infants and children, and are often caused by respiratory syncytial virus (RSV) or parainfluenza virus type 3 (PIV3), which may be responsible for $1 billion of medical costs and 10,000 deaths annually in the United States. There is no licensed vaccine for either virus, and the only licensed drug, Ribavirin(TM), is of limited efficacy. In Phase I activities we showed that topical antibody caused clearance of virus without decreasing lesions. Triamcinolone acetonide alone cleared the lung lesions, but resulted in a 10-fold increase of virus, wile both together sterilized the lung and reversed lesions. In the Phase II work, we will test four glucocorticosteroids with enhanced mucosal and decreased systemic activity. We will then examine the potential breadth of this therapeutic approach by treating cotton rats with established RSV (enveloped, RNA) and adenovirus type 5 (non-enveloped, DNA) viral pneumonia. The mechanism of action of glucocorticosteroids in reversing the lesions of viral pneumonia will be assessed in a mouse model of adenovirus pneumonia. We anticipate initiating clinical trials immediately upon completion of the proposed Phase II workscope. PROPOSED COMMERCIAL APPLICATION : Presently there is no effective therapy for established viral bronchiolitis and pneumonia. Topical therapy with a combination of antiviral antibody and glucocorticosteroid was shown to be effective and safe in Phase I work, and we will extend this to two additional viral pneumonias in Phase II.