Epidemiology and Immunobiology of HSV Infection

HSV 感染的流行病学和免疫生物学

• 批准号: 6221263
• 负责人: CHARLES G PROBER
• 金额: $ 14.58万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2003-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6221263
• 关键词: African American; adolescence (12-20); antibody formation; clinical research; communicable disease transmission; cooperative study; cytokine; epidemiology; helper T lymphocyte; herpes simplex virus 1; herpes simplex virus 2; human subject; leukocyte activation /transformation; microorganism immunology; protein biosynthesis; serology /serodiagnosis; sex behavior; sex partner; sexually transmitted diseases

There are limited data regarding the prevalence of HSV-2 infections among US adolescents. In addition, the functional mechanism and molecular targets of the initial immune responses that provide the foundation for controlling infection and promoting pathogenesis is largely unknown. Examining infection in adolescents who are presumably more immunologically "naive" and more likely to be diagnosed with a primary infection, compared to older individuals provides an important for evaluating the interaction among factors related to initial acquisition of infection, transmission, or progression to more severe sequelae including recurrent ulcers. Thus, adolescents present a unique opportunity to examine those factors which have direct relevance to vaccine development and treatment. Determining the prevalence of HSV-1 infection among adolescents and the interrelationship, if any, between seroprevalence of HSV-1 and HSV-2 will provide further important information regarding optimal HSV vaccine strategies. Specifically our aims are: 1. To determine sociodemographic and behavioral risk factors for prevalent and incident HSV-1 and HSV-2 infection among sexually active African-American adolescents. 2. To determine the natural history of cellular mediated immune responses in relation to clinical manifestations of HSV among infected individuals. We will assess the CD4 T-cell recognition of glycoproteins common to HSV-1 and HSV-2 (gB and gD), the type-specific gG2 protein and HSV-infected cell antigen, along with the Th1 and Th2 cytokine responses to stimulation with these antigens. 3. To determine immunologic risk factors for transmission of HSV-2 between adolescents and their sex partners over the course of the study among couples who are discordant on their HSV-2 serologic status. Transmission patterns will be assessed using gG2-based type-specific serologic assay, and then correlated with clinical histories of HSV infection, antibodies to heterologous virus, and duration of relationships.

关于美国青少年中HSV-2感染的流行率的数据有限。此外，为控制感染和促进发病提供基础的初始免疫反应的作用机制和分子靶点在很大程度上尚不清楚。与年长的人相比，检查那些在免疫学上更幼稚、更有可能被诊断为原发感染的青少年的感染，为评估与最初感染、传播或进展为更严重后遗症(包括复发性溃疡)相关的因素之间的相互作用提供了重要的参考。因此，青少年提供了一个独特的机会来检查那些与疫苗开发和治疗直接相关的因素。确定青少年中HSV-1感染的流行率，以及HSV-1和HSV-2血清阳性率之间的相互关系，将为最佳HSV疫苗策略提供进一步的重要信息。我们的具体目标是：1.确定性行为活跃的非裔美国青少年中流行和发生HSV-1和HSV-2感染的社会人口学和行为危险因素。2.探讨单纯疱疹病毒感染者细胞免疫应答的自然病程与临床表现的关系。我们将评估CD4T细胞对HSV-1和HSV-2共有的糖蛋白(GB和GD)、类型特异性GG2蛋白和HSV感染细胞抗原的识别，以及Th1和Th2细胞因子对这些抗原刺激的反应。3.在研究过程中，对于HSV-2血清学状态不一致的夫妇，确定在青少年和他们的性伴侣之间传播HSV-2的免疫危险因素。将使用基于GG2的类型特异性血清学试验评估传播模式，然后将其与HSV感染的临床病史、异源病毒抗体和关系持续时间相关联。