ANTIGEN PRESENTING VEHICLES IN HSV AND HIV INFECTIONS

HSV 和 HIV 感染中的抗原呈递载体

基本信息

批准号：
3547534
负责人：
THOMAS C MERIGAN
金额：
$ 16.38万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-08-15 至 1992-07-31
项目状态：
已结题

项目摘要

The long term goal of this research proposal is to design an effective and safe vaccine adjuvant for human administration. Specifically, we will study the adjuvant effects of liposome carriers containing an immunomodulator, muramyltripeptide-phosphatidyl-ethanolamine (MTP-PE). We have observed a markedly enhanced presentation, in vitro, of the antigen, HSV recombinant glycoprotein D (rgD), leading to in vivo immunotherapeutic effects in recurrent herpes simplex genitalis in guinea pigs. We will optimize the variables for use of these liposomes (collectively called antigen presenting liposome, APL) with HSV recombinant proteins, specifically rgD and rgB for immunotherapeutic treatment of HSV infection. Such variables include the use of various types of carriers, immunomodulators and variations in the antigen structure for the optimum adjuvant effect of antigen presenting vehicles (APV). In order to design an effective adjuvant, it is important to understand the immune mechanisms by which APV enhance immunotherapeutic effects. Therefore, we will elucidate the pathways by which APL (with MTP-PE) potentiate adjuvant effects of our HSV recombinant antigen. These studies will probe the immunotherapeutic effects in vivo, using the guinea pig model, and in vitro, using both guinea pig and human lymphocytes. The findings from this work will be utilized in designing an effective and safe adjuvant for HIV proteins. Since the enhancement of lymphocyte stimulation provided by APL in vitro parallels and improved clinical efficacy in the guinea pig HSV recurrence model, we propose to evaluate the adjuvant activities of the APV on the peripheral blood lymphocytes isolated from asymptomatic HIV-infected patients using molecularly cloned HIV antigens. Parallel experiments will also be done with HIV-infected chimpanzees that exhibit cellular immune responses to HIV antigens.

该研究建议的长期目标是设计有效的和人类行政管理的安全疫苗佐剂。具体来说，我们将研究含有脂质体载体的佐剂作用免疫调节剂，穆拉米酰三肽 - 磷脂酰乙醇胺（MTP-PE）。我们已经观察到了体外的明显增强的表现抗原，HSV重组糖蛋白D（RGD），导致体内复发性疱疹生殖器中的免疫治疗作用豚鼠。我们将优化使用这些脂质体的变量（统称称为抗原呈现脂质体，APL）用HSV 重组蛋白，特别是RGD和RGB，用于免疫治疗 HSV感染的治疗。这样的变量包括使用各种携带者的类型，免疫调节剂和抗原的变化抗原呈现车辆的最佳佐剂作用的结构（APV）。为了设计有效的佐剂，重要的是了解APV增强免疫治疗的免疫机制效果。因此，我们将阐明APL的途径（与我们的HSV重组抗原的MTP-PE）辅助作用。这些研究将使用体内探测体内的免疫治疗作用豚鼠模型和体外，同时使用豚鼠和人类淋巴细胞。这项工作的发现将用于设计一种有效且安全的HIV蛋白佐剂。自增强以来 APL在体外相似之处提供的淋巴细胞刺激和在豚鼠HSV复发模型中提高了临床功效，我们建议评估APV在外围的辅助活动使用无症状HIV感染患者分离的血液淋巴细胞使用分子克隆的HIV抗原。并行实验也将进行与艾滋病毒感染的黑猩猩表现出细胞免疫反应艾滋病毒抗原。