A NHP model for vaginal Zika Virus transmission

寨卡病毒阴道传播的 NHP 模型

• 批准号: 9255998
• 负责人: CHRISTOPHER James MILLER
• 金额: $ 31.22万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9255998
• 关键词: Adult; Animal Model; Animals; Antibody Response; Antiviral Agents; Arthralgia; Biological Assay; Biology; Brain; Brazil; Caribbean region; Centers for Disease Control and Prevention (U.S.); Central America; Coitus; Conjunctivitis; Country; Culicidae; Development; Disease Outbreaks; Dose; Enzyme-Linked Immunosorbent Assay; Exanthema; Exposure to; Female; Fever; Flaviviridae; Flavivirus; Flow Cytometry; Frequencies; Genital system; Goals; Health; Hour; Human; Immune; Immune response; Immunology; Infant; Infection; Irrigation; Lesion; Macaca; Macaca mulatta; Messenger RNA; Microcephaly; Modeling; Mus; Nature; Neurologic; Pathogenesis; Peripheral Blood Mononuclear Cell; Plasma; Pregnancy; Proteins; Publishing; Reporting; Research; Route; Sampling; Seminal fluid; Sentinel; Sexual Transmission; South America; Staining method; Stains; Symptoms; Syndrome; T cell response; Testing; Time; Tinnitus; Uganda; Urine; Vaccines; Vagina; Virus; Virus Diseases; Woman; World Health Organization; Zika Virus; adaptive immunity; antiviral immunity; cervicovaginal; cytokine; forest; hearing impairment; lissencephaly; male; men; nonhuman primate; pandemic disease; prevent; public health emergency; reproductive tract; transmission process; viral transmission; virology

Zika virus (ZIKV) (Flaviviridae, flavivirus), an emerging mosquito-borne virus, was first detected in Brazil in 2015 and has since spread to at least 38 countries in South America, Central America and Caribbean. The World Health Organization declared the ZIKV pandemic a public health emergency on February 1, 2016. In approximately 20% of infected humans, ZIKV causes a febrile illness that can include rash, arthralgia and conjunctivitis. In addition, ZIKV has been associated with the development of microcephaly and lissencephaly and ocular lesions in infants born to women who acquired ZIKV infection during early pregnancy. In adults, ZIKV has also been associated with Guillan-Barré syndrome and other neurological complications including hearing loss and tinnitus. Very little research has been done with ZIKV and our understanding of the virology, immunology and pathogenesis of ZIKV disease in humans is very limited. There are no established animal models, although a few studies have been imitated in the past few months. (NHP), and until February 2016, no NHP had been inoculated with contemporary pandemic ZIKV isolates. Although ZIKV is a mosquito-transmitted virus, reports of women becoming infected through sexual intercourse with ZIKV infected men have come from countries with no evidence of mosquito transmission. In fact, during February 6–22, 2016, health officials from several states reported two confirmed and four probable cases of ZIKV sexual transmission to CDC. In all cases, condomless vaginal intercourse occurred when the male partner was symptomatic or shortly after symptoms resolved. In addition, there are earlier reports suggesting ZIKV sexual transmission prior to the current outbreak, ZIKV virus has been found in semen and a recent report suggested ZIKV persists in semen for more than 60 days after onset of symptoms. Despite these observations the frequency and efficiency of sexual ZIKV transmission is unclear. To better understand the potential for sexual transmission of ZIKV and to test whether vaccines can prevent ZIKV transmission by this route an animal model is needed. The goal of this R21 is to develop a NHP model of vaginal ZIKV transmission. We will conduct initial studies to determine the efficiency of vaginal ZIKV transmission and characterize the virology of the infection. Further, we will characterize and compare innate and adaptive immune responses to ZIKV in the genital tract and systemic compartment.

寨卡病毒(ZIKV)(黄病毒科，黄病毒)是一种新出现的蚊媒病毒，于#年在巴西首次发现 自2015年以来，已经蔓延到南美洲、中美洲和加勒比海至少38个国家。这个 2016年2月1日，世界卫生组织宣布ZIKV大流行为公共卫生紧急状态。在……里面 在大约20%的感染者中，ZIKV会导致一种发烧疾病，包括皮疹、关节痛和 结膜炎。此外，ZIKV与小头畸形的发生和发展有关 早期感染寨卡病毒的妇女所生婴儿的无脑和眼部损害 怀孕了。在成人中，ZIKV也与格林-巴利综合征和其他神经系统疾病有关 并发症包括听力损失和耳鸣。对ZIKV和我们的 对人类寨卡病毒病的病毒学、免疫学和发病机制的了解非常有限。 目前还没有确定的动物模型，尽管在过去的几个月里已经有一些研究被模仿。 (NHP)，在2016年2月之前，没有NHP接种过当代大流行ZIKV分离株。 虽然ZIKV是一种蚊子传播的病毒，但有报道称女性通过性行为感染 与寨卡病毒感染者发生性行为的人来自没有蚊子传播证据的国家。在……里面 事实上，在2016年2月6日至22日期间，几个州的卫生官员报告了两起确诊病例和四起 寨卡病毒性传播到疾控中心的可能病例。所有病例均发生无避孕套的阴道性交。 当男性伴侣出现症状时或症状缓解后不久。此外，还有更早的 报告显示，在当前疫情爆发之前，ZIKV病毒在性传播中已被发现 精液和最近的一份报告表明，寨卡病毒在发病后在精液中持续存在60天以上 症状。尽管有这些观察，但性传播ZIKV的频率和效率尚不清楚。 为了更好地了解寨卡病毒的性传播潜力，并测试疫苗是否可以预防 通过这种途径传播ZIKV需要一个动物模型。这款R21的目标是开发NHP模型 经阴道传播的寨卡病毒。我们将进行初步研究，以确定阴道ZIKV的有效性 并确定感染的病毒学特征。更进一步，我们将描述和比较先天的 生殖道和全身器官对ZIKV的获得性免疫反应。