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

描述（由申请人提供）：这K23患者导向的职业发展奖申请是布伦娜安德森，医学博士，安德森博士是一位母胎医学专家，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的目的是发展一个独立的研究职业生涯艾滋病毒的妇女，重点是艾滋病毒感染的风险在怀孕期间。它将解决跨国家卫生研究院计划艾滋病毒相关的研究，为妇女和女孩的目标：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艾滋病毒传播的过程中的机制，收购，并抵抗感染妇女和女孩在整个生命周期。培训计划涉及四个重点领域：！获得艾滋病毒护理方面的专业知识，因为它适用于研究协议，2。* 培训妇女和少数民族特有的艾滋病毒临床研究课题，3.获得与HIV相关的生殖免疫学知识和转化研究，以及4.专业发展的正规培训。安德森博士将获得必要的技能，发展一个独立的研究计划。该研究计划将使用TZM-bl体外感染性试验确定未感染孕妇的HIV感染风险。将入组37例妊娠和37例非妊娠女性的前瞻性队列研究，并进行连续宫颈阴道灌洗采集。本研究的目的是表明，保护对艾滋病毒感染在怀孕期间减少，由于减少内源性抗菌成分在生殖器免疫道在怀孕期间，假设要测试的是，宫颈阴道灌洗（CVL）的孕妇将抑制艾滋病毒感染的程度低于非孕妇。研究的主要目的是1。在TZM-bl测定中比较来自妊娠和非妊娠妇女的CVL的抗HIV性质，以及2.鉴定并定量CVL中负责抑制感染性试验的内源性先天免疫抗病毒药。第二个目标是3。检查细菌性阴道病形式的正常阴道植物群破坏对HIV感染性的影响，4：评价宿主人种/种族对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会增加，其影响包括母婴传播艾滋病毒的可能增加。必须阐明妊娠期异性性传播的关键因素，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开发妊娠期杀微生物剂。

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.