The Role of Mucosal Immunity in the Risk of HIV-1 Acquisition During Pregnancy

描述（由申请人提供）：这个K23患者导向的职业发展奖申请是为Brenna Anderson， m.d., m.s.。Anderson博士是一名母胎医学专家，在临床研究和生殖传染病方面接受过额外的培训。安德森博士的培训和研究计划旨在发展妇女艾滋病毒的独立研究事业，重点关注怀孕期间艾滋病毒感染的风险。它将解决妇女和女孩艾滋病毒相关研究的跨nih计划的目标：阐明艾滋病毒传播的生物学决定因素，并确定病毒、宿主和免疫因素可能影响妇女和女孩整个生命周期中艾滋病毒传播、获取和感染抵抗过程的机制。培训计划包括四个重点领域：！获得艾滋病毒护理方面的专业知识，因为它适用于研究方案；2 .妇女和少数民族特有的艾滋病毒临床研究专题培训；3 .获取与HIV相关的生殖免疫学知识和转化研究；专业发展方面的正式培训。安德森博士将获得必要的技能，发展一个独立的研究项目。该研究计划将使用TZM-bl体外感染性试验确定未感染的孕妇感染艾滋病毒的风险。一项前瞻性队列研究将纳入37名孕妇和37名非孕妇，并进行连续的宫颈阴道灌洗收集。这项研究的目的是表明，由于怀孕期间生殖器免疫系统内的内源性抗菌成分减少，怀孕期间对艾滋病毒感染的保护能力降低。要验证的假设是孕妇的宫颈阴道灌洗（CVL）对HIV感染的抑制程度低于非孕妇。主要的研究目标是：1。比较孕妇和非孕妇CVL在TZM-bl和2中的抗hiv特性。鉴定和量化内源性先天免疫抗病毒病毒在CVL负责抑制感染性试验。第二个目标是3。研究细菌性阴道病对正常阴道菌群的破坏对HIV感染的影响；评估宿主种族/民族对CVL抗HIV特性的影响。公共卫生相关性：

DESCRIPTION (provided by applicant): This K23 patient oriented career development award application is for Brenna Anderson, M.D., M.Sc. Dr. Anderson is a Maternal Fetal Medicine specialist with additional training in clinical research and reprodcutive infectious diseases. Dr. Anderson's training and research plans are designed to develop an independent research career on HIV in women with a focus on risk of HIV acquisition in pregnancy. It will address the trans-NIH plan for HIV-related research for Women and Girls objective: To elucidate biologic determinants of HIV transmission and define the mechanisms by which viral, host, and immune factors may influence the process of HIV transmission, acquisition, and resistance to infection among women and girls across the life cycle. The training plan involves four focus areas:! gaining expertise in HIV care as it applies to research protocols, 2. training in clinical HIV research topics that are unique to women and minorities, 3. acquisition of knowledge in reproductive immunology relevant to HIV and translational research, and 4. formal training in professional development. Dr. Anderson will acquire the necessary skills develop an independent research program. The research plan will determine the risk of HIV infectivity among uninfected pregnant women using a TZM-bl in vitro infectivity assay. A prospective cohort study of 37 pregnant and 37 non-pregnant women will be enrolled and followed with serial cervicovaginal lavage collections. The study goal is to show that protection against HIV infection during pregnancy is reduced due to decreased endogenous antimicrobial components in the genital immune tract during pregnancy.The hypothesis to be tested is that the cervicovaginal lavage (CVL) of pregnant women will inhibit HIV infectivity to a lesser extent than that of non-pregnant women. The primary study aims will be 1. To compare anti-HIV properties of CVL from pregnant and non-pregnant women in a TZM-bl assay and 2. To identify and quantify the endogenous innate immune antivirals in the CVL responsible for inhibition of the infectivity assays. The secondary aims will be 3. To examine the impact that disruption of normal vaginal flora in the form of bacterial vaginosis has on HIV infectivity, and 4: To evaluate the impact of host race/ethnicity on the anti-HIV properties of CVL. PUBLIC HEALTH RELEVANCE: Pregnant women may be at increased risk for HIV acquisition and the implications of this include a possible increase in mother to child HIV transmission. Key factors in heterosexual transmission in pregnancy must be elucidated to develop preventive measures that are safe and effective in pregnant women. Endogenous components of the immune system could be used in development of microbicides during pregnancy.