derG Immunostimulant Prevention/Treatment of HSV Disease

描述(由申请人提供)：该计划的目标是开发DERG作为治疗和/或预防单纯疱疹病毒感染的药物。DERG是一种小肽，在初步实验中显示可以引起抗病毒和抗寄生虫(疟疾)反应，以及佐剂活性。根据它的结构，DERG应该能与CD4分子结合。其广泛的活性表明，它对先天或获得性免疫系统在抗原攻击之前的早期事件具有新的作用。这种名为DERG的药物将用于治疗医学上重要的病毒和其他感染，这些感染可能没有治疗方法或疫苗，或者治疗毒性太大或疗效有限。这种具有免疫增强或佐剂活性的多肽或类似的多肽将被评估为潜在的临床候选药物，以提供对其他无法治疗的感染性病原体的广谱保护。在旅行或被分配到暴露的高风险区域之前，或在初次接触之后，例如性传播疾病或其他传染病病原体，这可能是有用的。这项研究的努力将集中在单纯疱疹病毒上，认识到由此产生的结果可能是一种也将作为预防或治疗药物应用于其他传染病的药物。第一阶段的具体目标如下：在活体活动中：评估DERG在单纯疱疹病毒1型疾病动物模型中提供的保护作用，作为路线(皮下、腹膜、肌肉内)、剂量和载体(生理盐水或乳剂)以及DERG给药的时间的函数，以优化治疗，以实现未来的特定目标。具体目的2.通过疾病的鳞片状传播模型，确定负责启动和介导DERG诱导的保护的细胞类型(先天、诱导和效应)以及在HSV攻击期间发生保护的机制(细胞因子释放)。证明在不同的单抗或表面受体阻断试剂处理后，表达CD4、CD8、CD86(B7-1)、CD80(B7-2)和CD40的细胞的重要性。如果成功，第二阶段计划将在HSV生殖器感染模型中评估DERG，并在近交系和近交系动物中测试DERG对HSV I和HSV II株的影响。第二阶段计划的一个组成部分将是进一步阐明DERG的靶细胞和作用机制。

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.