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

描述(由申请人提供)：这份K23面向患者的职业发展奖申请是针对Brenna Anderson，M.D.，M.Sc。安德森博士是一名母胎医学专家，在临床研究和再生性传染病方面接受过额外培训。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生涯，重点放在怀孕期间感染艾滋病毒的风险上。它将讨论妇女和女孩艾滋病毒相关研究的跨NIH计划目标：阐明艾滋病毒传播的生物决定因素，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、感染和抵抗感染的过程的机制。该培训计划涉及四个重点领域：获得艾滋病毒护理方面的专门知识，因为它适用于研究方案；2.妇女和少数群体特有的艾滋病毒临床研究专题的培训；3.获得与艾滋病毒有关的生殖免疫学知识和转化研究；以及4.专业发展方面的正式培训。安德森博士将获得必要的技能，制定一个独立的研究计划。该研究计划将使用TZM-bl体外传染性试验来确定未感染的孕妇感染艾滋病毒的风险。一项针对37名孕妇和37名未怀孕妇女的前瞻性队列研究将被纳入，随后进行一系列的宫颈阴道灌洗。这项研究的目的是证明，由于怀孕期间生殖器免疫道中内源性抗菌成分的减少，对怀孕期间感染艾滋病毒的保护作用减弱。有待检验的假设是，孕妇的宫颈阴道灌洗(CVL)对艾滋病毒感染的抑制程度低于未怀孕妇女。本研究的主要目的是：1.用TZM-bl法比较孕妇和非孕妇女CVL的抗HIV特性；2.鉴定和定量CVL中负责抑制感染性试验的内源性天然免疫抗病毒药物。第二个目标将是3.检查以细菌性阴道病的形式破坏正常阴道菌群对HIV感染性的影响，以及4：评估宿主种族/民族对CVL抗HIV特性的影响。公共卫生相关性： 孕妇感染艾滋病毒的风险可能增加，其影响包括母婴传播艾滋病毒的可能增加。必须阐明孕期异性传播的关键因素，以制定对孕妇安全有效的预防措施。免疫系统的内源性成分可用于孕期杀菌剂的开发。

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.