Transmission Correlates

传输相关性

• 批准号: 8375407
• 负责人: DOUGLAS D RICHMAN
• 金额: $ 107.36万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-15 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8375407
• 关键词: Accounting; Address; Adjuvant; Affect; Antibody Formation; Antigens; B-Lymphocytes; Base Sequence; Behavioral; Biological; Biological Assay; Blood; CD4 Positive T Lymphocytes; CD8B1 gene; Cells; Cellular Immunity; Cellular Tropism; Characteristics; Chlamydia; Clinical; Collaborations; Computational Technique; Constitution; Containment; Cytomegalovirus; Data; Disease; Epidemiology; Epitopes; Exhibits; Genes; Genetic; Genetic Markers; Genital system; Gonorrhea; HIV; HIV Infections; HIV-1; Health Sciences; Human Herpesvirus 2; Human Papillomavirus; Individual; Infection; Integration Host Factors; Intervention; Laboratories; Length; Lymphocyte; Lymphocyte Count; Male Circumcision; Measures; Mediating; Mononuclear; Mutation; Pattern; Phenotype; Plasma; Predisposition; Prevention strategy; Principal Investigator; Probability; Publishing; RNA; Reporter; Reporting; Research; Research Project Grants; Resistance; Resources; Risk; Role; Satellite Viruses; Sexual Transmission; Sexually Transmitted Diseases; Source; Specimen; Staging; Study Subject; Syphilis; System; T cell response; T-Lymphocyte Epitopes; Testing; Texas; Universities; Vaccine Design; Vaccines; Variant; Viral; Viral Load result; Virus; Walkers; base; chemokine; cofactor; data management; design; fitness; genetic element; genital secretion; genome sequencing; improved; indexing; insight; medical schools; neutralizing antibody; population based; programs; response; transmission process; vaccine candidate; vaccine evaluation; virus genetics

Project 2 (Transmission Correlates) will characterize the biological, viral, and host correlates of HIV sexual transmission. The Clinical and Specimen Core will identify study subjects and provide the blood and genital secretion specimens for the research projects. Project 1 (Transmission Probability) will ascertain rates of transmission and generate epidemiological and behavioral data. The Administrative Core will coordinate these activities together with data management, and provide the statistical and analytical resources to permit robust and valid conclusions regarding the data. Aim 1 of Project 2 will measure the biologic correlates of sexual transmission of HIV. These include viral loads in blood and the genital tract, lymphocyte numbers in genital secretions, and the presence of viral and bacterial sexually transmitted infections. This aim will also address whether sexually transmitted HIV infection is mediated by cell-free virus or by virus-infected lymphocytes. Aim 2 will assess the viral correlates of sexual transmission of HIV. Extensive nucleotide sequencing will extend our published observations characterizing virus in the genital compartment. The objective will be to characterize the genotypic and phenotypic characteristics of transmitted HIV-1 variants. Aim 3 will investigate host determinants of sexual transmission of HIV. We will extend our studies of the neutralizing antibody response to HIV infection by determining the role of neutralizing antibody in blood and the genital tract in selecting for transmitted viral variants. The other two components of the aim will leverage our well characterized study subjects and their clinical specimens with two internationally recognized laboratories with longstanding collaborations with our group. Dr. Sunil Ahuja from the University of Texas Health Sciences Center will characterize the host genetics of both index subjects and their transmitting partners. Drs. Walker, Allen, and Altfeld from Harvard Medical School will provide full length HIV genome sequencing, viral phenotype, and CTL analyses that will characterize the role of cell mediated immunity, escape, and fitness. Each of these Aims is designed to address specific hypotheses. The data collected in Project 2, together with the epidemiologic and behavioral data from Project 1, will permit comprehensive analyses to determine which parameters are confounding, dependent, or independent determinants of HIV sexual transmission. These insights should provide important leads into the design of better vaccine candidates and other preventive strategies.

项目2（传播相关性）将描述艾滋病毒的生物学、病毒和宿主相关性 性传播临床和标本中心将确定研究受试者，并提供血液和 生殖器分泌物标本的研究项目。项目1（传输概率）将确定 传播率，并生成流行病学和行为数据。行政核心将 协调这些活动与数据管理，并提供统计和分析 资源，以便对数据得出可靠且有效的结论。 项目2的目标1将衡量艾滋病毒性传播的生物相关因素。其中包括病毒 血液和生殖道中的载量，生殖器分泌物中的淋巴细胞数量，以及病毒和 细菌性性传播感染这一目标还将解决性传播艾滋病毒是否 感染由无细胞病毒或由病毒感染的淋巴细胞介导。 目标2将评估艾滋病毒性传播的病毒相关性。广泛核苷酸测序 将扩展我们发表的观察结果，描述生殖器隔室中的病毒。这一目标的方式是 以表征传播的HIV-1变异体的基因型和表型特征。 目标3将调查艾滋病毒性传播的宿主决定因素。我们将继续研究 通过确定血液中中和抗体的作用， 生殖道在选择传播的病毒变异。该目标的其他两个组成部分将利用 我们充分表征的研究对象及其临床标本具有两种国际公认的 与我们集团长期合作的实验室。德克萨斯大学的Sunil Ahuja博士 健康科学中心将描述两个指标受试者的宿主遗传学及其传播 伙伴来自哈佛医学院的步行者、艾伦和阿尔特菲尔德博士将提供全长艾滋病毒基因组 测序、病毒表型和CTL分析将表征细胞介导的免疫的作用， 逃生和健身 这些目标中的每一个都旨在解决特定的假设。项目2中收集的数据， 与项目1的流行病学和行为数据一起，将允许进行全面的分析， 确定哪些参数是HIV性传播的混杂、依赖或独立决定因素 传输这些见解应该为设计更好的候选疫苗提供重要的线索 以及其他预防策略。