STUDIES OF GLYCOPROTEIN D OF HERPES SIMPLEX VIRUS

拟议调查的目标是进行详细的 普通型信封的生化和免疫学研究 L型单纯疱疹病毒糖蛋白D(口服)和单纯疱疹病毒2型 (生殖器形式)。GD的多种结构和免疫学特性 表明它是考虑作为一个亚单位的一个重要候选者 疫苗。我们计划定位、构建和表征抗原性 GD的决定因素。我们将对来自一株 努力确定更多的gd表位的实验室数量。 抗体将针对来自GD的各种片段进行测试， 以便于绘制地图。此外，合成的多肽对应于 将合成并测试特定表位的可能位置 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。单抗 将对抗性(Mar)突变体进行分析，以努力进一步定位 GD表位。建议进行实验以确定数量和位置 广东-L和广东-2中的二硫桥。这些研究将具有重要意义。 了解GD的二级和三级结构的各个方面。 这些结构研究将使我们能够了解 构象表位。GD-L和GD-2的制备及碎片 从这些蛋白质中提取的蛋白质将被评估其保护能力 在一个小鼠病毒挑战模型系统中。我们将评估两国关系 中和抗体刺激与致死保护之间的关系 病毒挑战。这笔拨款中建议的研究将允许 对糖蛋白D或其衍生物的有用性进行评估 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.