Foreskin Mucosal Cellular Constituents & Effects of Circumcision on HIV/STI Risk

包皮粘膜细胞成分

• 批准号: 8318248
• 负责人: Kristine E Johnson
• 金额: $ 13.43万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8318248
• 关键词: AIDS prevention; Adult; Africa; Africa South of the Sahara; Anatomy; Appointment; Archives; Area; Autoimmune Diseases; Baltimore; Cell surface; Cells; Cervical; Clinical; Clinical Research; Clinical Skills; Clinical Trials; Cohort Studies; Collaborations; Communicable Diseases; Communication; Communities; Confocal Microscopy; Country; Cutaneous Melanoma; Data; Data Analyses; Databases; Dermal; Dermatologic; Development; Disease; Doctor of Philosophy; Enrollment; Epidemiologist; Epidemiology; Epithelial; Evaluable Disease; Event; Faculty; Family health status; Fellowship; Female; Functional disorder; Future; Grant; Gray unit of radiation dose; HIV; Health Sciences; Health education; Heterosexuals; Histology; Human Herpesvirus 2; Human Papillomavirus; Immune; Immune response; Immunohistochemistry; Immunologic Monitoring; Immunologist; Immunology; Infection; Infection prevention; Inflammation; Inflammatory; International; Intervention; Investigation; Joints; Laboratories; Laboratory Finding; Lead; Link; Lymphocyte; Male Circumcision; Manuscripts; Medical Microbiology; Medical center; Medicine; Mentors; Mentorship; Methods; Mid-Career Clinical Scientist Award (K24); Modality; Molecular Epidemiology; National Institute of Allergy and Infectious Disease; Natural History; Neoplasms; Operative Surgical Procedures; Outcome; Paper; Parents; Pathogenesis; Pathology; Pattern; Peer Review; Persons; Physicians; Population; Postdoctoral Fellow; Preparation; Prevention; Principal Investigator; Productivity; Protocols documentation; Public Health; Public Health Schools; Publishing; Quality Control; Randomized Clinical Trials; Randomized Controlled Trials; Reproductive Health; Research; Research Personnel; Research Project Grants; Research Training; Resources; Risk; Role; Sampling; Science; Scientist; Serum; Sex Behavior; Sexual Health; Sexually Transmitted Diseases; Site; Specimen; Structure; Students; T-Cell Lymphoma; Techniques; Time; Tissues; Training; Translational Research; Uganda; United States National Institutes of Health; Universities; Viral; Virus; Work; abstracting; authority; base; career; cytokine; design; doctoral student; epidemiologic data; follow-up; global health; immunopathology; indexing; inflammatory marker; interest; male; meetings; member; men; novel; penis foreskin; population health; professor; programs; prospective; repository; reproductive epidemiology; sex; skills; transmission process; tumor; validation studies; virology

DESCRIPTION (provided by applicant): HIV in sub-Saharan Africa is almost exclusively transmitted by heterosexual sex. Prospective randomized clinical trials (RCTs) in Africa, including 2 conducted by Hopkins researchers in Uganda, demonstrate that adult male circumcision reduces HIV acquisition by 60% and herpes simplex virus-2 (HSV-2) acquisition." Little is known about the immunology and pathophysiology of the foreskin. We propose to describe the immunology of foreskin inflammation and assess its role in HIV and HSV-2 acquisition and transmission using data and foreskin specimens obtained from the circumcision RCTs. The Hopkins Uganda circumcision trials enrolled both HIV+ and HIV--index male subjects and their female partners and archived the surgical foreskin specimens. With this repository, we have a unique opportunity to evaluate this hypothesis and to understand inflammation in the foreskin. The K23 candidate, Dr. Kristine Johnson, has specific interests in HIV immunology and sexually transmitted infections. The proposal provides for structured training and mentorship support to develop a translational research program to explore these relationships. Using methods already developed by Dr. Johnson, she will define local lymphocyte populations within the foreskin tissues, by confocal microscopy and immunohistochemistry. Using tissue PCR, she will quantify and characterize associated inflammation patterns and tissue HIV and HSV-2 viral content. After this work is completed, using the rich data collected on index subjects and partners, she will assess the impact of the foreskin cellular components on HIV acquisition events among initially HIV-uninfected men and the impact of foreskin cellular and viral components on HIV transmission events to serodiscordant female partners. Kristine Johnson, MD, joined the faculty of Johns Hopkins University Division of Infectious Diseases in July 2008. This application integrates epidemiology and immunological approaches using a unique sample set to answer critical questions in HIV/HSV-2 transmission. There is an especially strong mentorship team of experts in HIV/STI transmission and prevention, including Drs. Jonathan Zenilman, Ronald Gray and Thomas Quinn. RELEVANCE: As a beginning, we propose here to evaluate relationships between foreskin inflammation, epithelial lymphocyte populations, cytokines and HIV and HSV-2 infection and transmission. The results of this work will lead to a better understanding of the male foreskin immune milieu and may inform the development of new modalities for targeted HIV and STI prevention.

描述（由申请人提供）：撒哈拉以南非洲地区的艾滋病毒几乎完全通过异性性行为传播。在非洲进行的前瞻性随机临床试验 (RCT)（其中包括由霍普金斯大学研究人员在乌干达进行的 2 项试验）表明，成年男性包皮环切术可减少 60% 的 HIV 感染和 2 型单纯疱疹病毒 (HSV-2) 感染。”我们建议描述包皮炎症的免疫学，并使用从包皮环切术中获得的数据和包皮标本评估其在 HIV 和 HSV-2 获取和传播中的作用。霍普金斯乌干达包皮环切试验招募了 HIV+ 和 HIV-指数男性受试者及其女性伴侣，并存档了手术包皮标本，通过这个存储库，我们有一个独特的机会来评估这一假设并了解包皮炎症。 K23 候选人 Kristine Johnson 博士对 HIV 免疫学和性传播感染特别感兴趣。该提案提供了结构化培训和指导支持，以开发转化研究计划来探索这些关系。 使用约翰逊博士已经开发的方法，她将通过共聚焦显微镜和免疫组织化学来定义包皮组织内的局部淋巴细胞群。她将使用组织 PCR 来量化和表征相关炎症模式以及组织中的 HIV 和 HSV-2 病毒含量。这项工作完成后，利用在指标对象和伴侣上收集的丰富数据，她将评估包皮细胞成分对最初未感染艾滋病毒的男性中艾滋病毒感染事件的影响，以及包皮细胞和病毒成分对艾滋病毒传播事件的影响血清不一致的女性伴侣。 Kristine Johnson 医学博士于 2008 年 7 月加入约翰霍普金斯大学传染病系。该应用程序集成了流行病学和免疫学方法，使用独特的样本集来回答 HIV/HSV-2 传播中的关键问题。在艾滋病毒/性传播感染和预防方面，有一支特别强大的专家指导团队，其中包括博士。乔纳森·泽尼尔曼、罗纳德·格雷和托马斯·奎恩。 相关性：首先，我们建议评估包皮炎症、上皮淋巴细胞群、细胞因子与 HIV 和 HSV-2 感染和传播之间的关系。这项工作的结果将有助于更好地了解男性包皮免疫环境，并可能为开发有针对性的艾滋病毒和性传播感染新方法提供信息。