Clinical Research in HSV Infections

HSV 感染的临床研究

• 批准号: 8662156
• 负责人: Anna Wald
• 金额: $ 18.29万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-15 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8662156
• 关键词: Acyclovir; Address; Adverse effects; Affect; Africa South of the Sahara; Anatomic Sites; Antiviral Agents; Antiviral Therapy; Area; Bacterial Vaginosis; Benign; Biopsy; CCR5 gene; CD209 gene; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; CD8B1 gene; Cells; Chronic; Clinical; Clinical Investigator; Clinical Research; Clinical Trials; Clinical Virology; Complex; Congenital herpes simplex; Counseling; Dendritic Cells; Dermal; Developed Countries; Diagnostic; Disease; Epidemiologic Studies; Epidemiology; Epithelial; Failure; Fostering; Frequencies; Funding; Gender; Genital system; Goals; Grant; HIV; Health; Herpesvirus 1; Human; Human Herpesvirus 2; IL3RA gene; IL8 gene; Immune; Immune response; Immunity; Immunocompetent; Immunocompromised Host; Immunologics; Immunosuppression; Infection; Inflammation Mediators; Knowledge; Lactoferrin; Maintenance; Manuscripts; Measures; Mediating; Mentored Patient-Oriented Research Career Development Award; Mentors; Metabolic Clearance Rate; Midcareer Investigator Award in Patient-Oriented Research; Morbidity - disease rate; Mucous Membrane; Muramidase; Natural History; Natural Immunity; Nerve Endings; Outcome; Patients; Persons; Pharmaceutical Preparations; Physicians; Population; Preparation; Publishing; Recurrence; Research; Research Personnel; Risk; Series; Sexual Partners; Simplexvirus; Site; Skin; Supervision; T-Lymphocyte; Therapeutic; Time; Training; Vaccines; Vagina; Virus; Virus Diseases; Virus Shedding; Woman; antileukoprotease; career; chemokine receptor; density; epidemiologic data; genital herpes; genital infection; human SLPI protein; human neutrophil peptide 1; improved; insight; interest; men; mortality; next generation; novel; pathogen; patient oriented research; receptor; research study; transmission process

DESCRIPTION (provided by applicant): The overarching goal of this Renewal K24 Midcareer Investigator Award in Patient-Oriented Research is to foster training of promising junior investigators in high quality Patient-Oriented Research in clinical virology, with a focus on HSV infections. During the first cycle of K24 funding, the PI achieved her original goals, increased the number of clinical investigators under her supervision, including several with K23 awards, and published 55 manuscripts first-authored by mentees. Additionally, Dr. Wald has expanded her research portfolio, and broadened the scope of her mentoring activities. Ongoing projects include translational, clinical, therapeutic, epidemiologic, and preventative research, as well as clinical trials of drugs and vaccines. Our group has shown that HSV-2 reactivates frequently in the genital tract and that these epithelial infections are rapidly cleared by host immunity. Using biopsies of genital mucosa, we have shown that HSV-2 infection is associated with a dense and persistent infiltrate of immune cells, many bearing HIV entry receptors. The funded projects have these Specific Aims: 1) To determine the frequency of rapidly cleared (<6 hrs) mucosal HSV-2 infections by gender and degree of immunosuppression; 2) To define the clearance rate of mucosal HSV reactivation in relation to locally infiltrating HSV-2-specific CD8+ T cells in genital skin at the anatomic site of reactivation. We hypothesize that the clearance of the shedding episode and time to next reactivation will correlate with the density of CD8+ cells at specific anatomic sites. The newly proposed projects include studies of genital HSV-1 and of interactions between HSV-2 and abnormal vaginal microbiota. Recent decade has seen a shift from HSV-2 to HSV-1 as the predominant cause of genital herpes in US. Yet natural history studies of this infection are lacking. The Specific Aim 3 will address these gaps by: A) determining the frequency of rapidly cleared (<6 hrs) mucosal HSV-1 infections in men and women with newly acquired (<6 months) and established (>2 years) genital HSV-1 infections; 2) evaluating the site of HSV infection in persons who transmitted genital HSV-1 infection to their partners. We hypothesize that > 50% of sex partners will have HSV-1 shedding from the genital tract, thus indicating the possibility of genital-to-genital HSV-1 transmission. Epidemiologic studies suggest an interaction between HSV and bacterial vaginosis; we will extend these pilot observations into clinical and mechanistic studies. Specific aim 4 will evaluate the effect of vaginal microbiota on HSV shedding and the effect of HSV suppression on vaginal microbiota. We hypothesize that these 2 conditions will have an adverse effect on each other, and that the effect will be mediated by soluble mediators of inflammation, such as secretory leukocyte protease inhibitor, human neutrophil peptides 1-3 and lactoferrin,. These carefully selected projects provide opportunities for training junior clinical investigators in high-quality Patient-Oriented Research and preparations for an investigative career in clinical virology.

描述（由申请人提供）：本次更新K24面向患者研究中期研究者奖的总体目标是培养有前途的初级研究者，从事高质量的临床病毒学面向患者的研究，重点是HSV感染。在K24资助的第一个周期中，PI实现了她最初的目标，增加了她所指导的临床研究者的数量，其中包括几位获得K23奖的临床研究者，并发表了55篇由学员第一作者撰写的论文。此外，她还扩大了她的研究组合，并扩大了她的指导活动的范围。正在进行的项目包括转化、临床、治疗、流行病学和预防研究，以及药物和疫苗的临床试验。