Modulation of innate immunity,microbiome and HIV transmission by Depo-Provera

Depo-Provera 对先天免疫、微生物组和 HIV 传播的调节

基本信息

批准号：
9045100
负责人：
Theresa L Chang
金额：
$ 2.11万
依托单位：
RBHS-NEW JERSEY MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-09 至 2018-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9045100
关键词：
AIDS prevention Accounting Adult African Androgens Animals Attenuated Vaccines Biological Process Biopsy Blood CCL2 gene CCR5 gene CD4 Positive T Lymphocytes CXCL10 gene Cell surface Cervical Contraceptive Agents Contraceptive Usage Country Data Depo Provera Development Diagnosis Ecosystem Endocervix Epidemiologic Studies Family Planning Feces Female Glucocorticoids Goals HIV HIV Infections Health Hormonal Hormones Host Defense Human Immune Immune response Immune system Immunologics In Vitro Infection Injectable Injection of therapeutic agent Integrins Lactobacillus Lead Longitudinal Studies Luteal Phase Macaca mulatta Mediating Mediator of activation protein Medroxyprogesterone 17-Acetate Methods Modeling Mucosal Immune Responses Mucous Membrane Natural Immunity Peripheral Play Police Predisposition Prevention strategy Progesterone Progestins Resources Risk Role SIV Sampling Sexual Transmission Sexually Transmitted Diseases Site Specimen Surveys T-Cell Activation T-Cell Depletion T-Lymphocyte T-Lymphocyte Subsets Taxon Testing Time Vagina Woman base birth control cervicovaginal chemokine design hormonal contraception immunoregulation in vivo insight microbiome proliferative phase Menstrual cycle pyrosequencing rRNA Genes response simian human immunodeficiency virus transmission process vaccine efficacy vaginal transmission young woman

项目摘要

DESCRIPTION (provided by applicant): Epidemiologic studies demonstrate that DMPA may increase the risk of HIV acquisition and transmission. Additionally, Depo-Provera has been shown to attenuate the vaccine efficacy to protect rhesus macaques against SIV infection. The impact of hormonal contraceptive use on HIV acquisition and transmission has profound implications for polices on family planning, particularly in countries with high rates of HIV transmission. While progesterone clearly enhances vaginal transmission of SIV/SHIV in rhesus macaques, the effect of progestin-based hormone on HIV acquisition/transmission in women remains unresolved. We hypothesize that injectable DMPA alters immune responses and cervicovaginal and colonic microbiomes, which may lead to increased HIV acquisition and transmission. The aims of this proposal are designed to (1) determine the impact of Depo-Provera on the systemic and mucosal immune systems and on cervicovaginal and colonic microbiomes in a longitudinal study, and (2) to elucidate the immune mechanisms of MPA-mediated modulation of HIV infection/transmission in vitro, ex vivo and in cervical explant models. Blood, cervicovaginal specimens and stool samples will be collected at baseline (both follicular and luteal phases) and after 4, and 8 weeks of DMPA injection. The immunological profiles of CD4+ T cells and their susceptibility to HIV will be characterized. We will determine the temporal impact of DMPA on cervicovaginal and colonic microbiome. Global alteration and changes in specific taxa will be correlated with immunological changes. The results of our studies will provide a better understanding of how DMPA modulates immunologic responses and microbiomes, thereby informing the design of effective HIV prevention strategies.

描述（由申请人提供）：流行病学研究表明，DMPA可能会增加艾滋病毒获取和传播的风险。此外，已证明Depo-Provera可衰减疫苗功效，以保护恒河猴免受SIV感染的影响。激素避孕药使用对艾滋病毒收购和传播的影响对政策对计划生育的影响有很大的影响，尤其是在艾滋病毒传播率高的国家中。虽然孕激素清楚地增强了恒河猕猴中SIV/SHIV的阴道传播，但基于孕激素激素对女性HIV获取/传播的影响仍未解决。我们假设可注射的DMPA改变了免疫反应以及宫颈阴道和结肠微生物组，这可能导致HIV的获取和传播增加。该提案的目的旨在（1）在一项纵向研究中确定depo-provera对系统和粘膜免疫系统以及对宫颈阴道和结肠微生物组的影响，（2）阐明了MPA介导的HIV介导的HIV感染的免疫机制。将在基线（卵泡和黄体阶段）以及DMPA注射4周后收集血液，宫颈阴道标本和粪便样品。 CD4+ T细胞的免疫学特征及其对HIV的敏感性将被表征。我们将确定DMPA对宫颈阴道和结肠微生物组的时间影响。全球变化和特定类群的变化将与免疫学变化相关。我们的研究结果将更好地了解DMPA如何调节免疫反应和微生物组，从而为有效的HIV预防策略设计。