derG Immunostimulant Prevention/Treatment of HSV Disease

derG 免疫刺激剂预防/治疗 HSV 疾病

• 批准号: 6643833
• 负责人: Daniel Hill Zimmerman
• 金额: $ 16.21万
• 依托单位: CEL-SCI CORPORATION
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6643833
• 关键词: antimalarial agents; antiviral agents; biotherapeutic agent; cell type; cytokine; drug administration rate /duration; drug administration routes; drug screening /evaluation; herpes simplex virus 1; immunomodulators; laboratory mouse; monoclonal antibody; peptides; pharmacokinetics; shingles

DESCRIPTION (provided by the applicant): The goal of this program is to develop derG as a therapeutic and/or prophylactic agent for HSV infections. DerG is a small peptide shown in preliminary experiments to elicit anti-viral and anti-parasitic (malarial) responses, and adjuvant activity. Based upon its structure, derG should bind to CD4 molecules. Its broad spectrum of activity suggests that it has a novel action on the innate or adaptive immune system's early events before antigenic challenge. This agent, derG, would be useful for treatment of medically important viral and other infections for which there may not be treatment or vaccine, or the treatment is too toxic or of limited efficacy. This peptide, or similar peptides, with immunoenhancing or adjuvant activity will be evaluated as potential clinical candidates to be used as a drug to provide broad spectrum protection against otherwise untreatable infectious agents. This may be useful prior to travel or assignment to a region of high risk for exposure or immediately after initial contact such as with sexually transmitted diseases or other infectious agents. Efforts in this study will focus on the herpes simplex viruses with the recognition that the resultant outcome may be an agent that will also have application for other infectious diseases as either a prophylactic or a therapeutic agent. The specific aims of the phase I are as follows: Specific Aim 1. In Vivo Activity: Evaluate the protection afforded by derG in animal models of HSV 1 disease as a function of the route (subcutaneous, intraperitoneal, intramuscular), dose amount and vehicle (saline or emulsion) and timing of derG administration to optimize treatment for the accomplishment of future specific aims. Specific Aim 2. Determine the cell types responsible for initiating and mediating derG induced protection (innate, inductive and effector) and the mechanism (cytokine release) by which protection occurs during HSV challenge by the scarification-zosteriform spread model of disease. Demonstrate the importance of CD4, CD8, CD86(B7-1), CD80 (B7-2), and CD40 expressing cells following treatment with various monoclonal antibody or surface receptor ablating-blocking reagents. If successful the phase II program will evaluate derG in a HSV genital infection model and test derG on HSV I and HSV II strains in both inbred and outbred animals. An integral part of the phase II program will be to further elucidate the target cells and mechanism of action of derG.

描述（由申请人提供）：这个项目的目标是开发derG作为治疗和/或预防HSV感染的药物。在初步实验中显示，DerG是一种小肽，可引起抗病毒和抗寄生虫（疟疾）反应，并具有佐剂活性。根据其结构，derG应该与CD4分子结合。其广泛的活性谱表明它在抗原攻击前对先天或适应性免疫系统的早期事件有新的作用。这种药物derG可用于治疗医学上重要的病毒感染和其他感染，这些感染可能没有治疗方法或疫苗，或者治疗方法毒性太强或疗效有限。这种具有免疫增强或辅助活性的肽或类似肽将被评估为潜在的临床候选药物，用于提供广谱保护，以抵抗其他无法治疗的感染因子。在前往或被派往高风险接触地区之前，或在初次接触（如性传播疾病或其他传染物）之后，这可能是有用的。本研究的工作将集中在单纯疱疹病毒上，并认识到最终的结果可能是一种药物，也将应用于其他传染病，作为预防或治疗药物。第一阶段的具体目标如下：体内活性：评估derG在HSV - 1疾病动物模型中提供的保护作用，作为途径（皮下、腹腔、肌肉注射）、剂量和载体（生理盐水或乳剂）以及derG给药时间的功能，以优化治疗，以实现未来的特定目标。具体目标2。确定负责启动和介导derG诱导的保护（先天、诱导和效应）的细胞类型，以及在HSV通过划痕-带状虫状传播模型攻击时发生保护的机制（细胞因子释放）。证明CD4、CD8、CD86（B7-1）、CD80 （B7-2）和CD40表达细胞在各种单克隆抗体或表面受体消融阻断试剂处理后的重要性。如果成功，第二阶段计划将在HSV生殖器感染模型中评估derG，并在近交系和远交系动物中测试derG对HSV I和HSV II菌株的影响。II期项目的一个组成部分将是进一步阐明derG的靶细胞和作用机制。