STUDIES OF GLYCOPROTEIN D OF HERPES SIMPLEX VIRUS

拟议调查的目的是进行详细的 普通型被膜的生化和免疫学研究 单纯疱疹病毒（HSV）I型（口服形式）和HSV-2的糖蛋白D （生殖器形式）。 gD的许多结构和免疫学性质 表明它是考虑作为子单元重要候选者 疫苗 我们计划定位，构建和表征抗原 gD的决定因素 我们将从一个 许多实验室致力于鉴定额外的gD表位。 将针对源自gD的各种片段测试抗体， 以便于绘图。 此外，合成肽对应于 将合成并测试特异性表位的可能位置 用于中和抗体的抗原性生产，以及 刺激小鼠的保护性免疫反应。 单克隆抗体 将分析抗性（mar）突变体，以进一步定位 gD表位。 实验提出了确定的数量和位置 gD-1和gD-2中的二硫键。 这些研究将具有重要意义 在理解gD的二级和三级结构方面。 这些结构研究将使我们能够了解 构象表位 gD-1和gD-2及片段的制备 将评估这些蛋白质的保护能力 在小鼠病毒攻击模型系统中。 我们将评估 中和抗体的刺激和对致死性 病毒挑战 这项补助金中提出的研究将允许 对糖蛋白D或其衍生物有用性的评估 刺激保护性免疫反应。

The objective of the proposed investigation is to carry out a detailed biochemical and immunological study of the type-common envelope glycoprotein D of herpes simplex virus (HSV) type l (oral form) and HSV-2 (genital form). Many structural and immunological properties of gD indicate that it is an important candidate for consideration as a subunit vaccine. We plan to localize, construct and characterize antigenic determinants of gD. We will characterize monoclonal antibodies from a number of laboratories in an effort to identify additional gD epitopes. Antibodies will be tested against a variety of fragments derived from gD, to facilitate mapping. In addition, synthetic peptides corresponding to the probable locations of specific epitopes will be synthesized and tested for antigenicity production of neutralizing antibody, and ability to stimulate a protective immune response in mice. Monoclonal antibody resistant (mar) mutants will be analyzed in an effort to further localize gD epitopes. Experiments are proposed to determine the number and location of disulfide bridges in gD-l and gD-2. These studies will be of importance in understanding aspects of the secondary and tertiary structure of gD. These structural studies will enable us to understand the nature of conformational epitopes. Preparations of gD-l and gD-2 and fragments derived from these proteins will be evaluated for their protective capacity in a mouse virus challenge model system. We will assess the relationship between stimulation of neutralizing antibody and protection against lethal virus challenge. The studies proposed in this grant will permit an assessment to be made of the usefulness of glycoprotein D or a derivative of it in stimulating a protective immune response.