Defining maternal and neonatal antibody responses in congenital Zika virus infection

摘要 候选人我的职业目标是改善先天性病毒感染儿童的健康， 探讨胎儿-母体免疫应答与先天性感染结局之间的关系。 我的短期目标是完善和增加我作为独立调查员的技能，并开始我的 作为一名年轻的教员，我在威斯康星州大学从事独立的研究工作， 在有限的时间和资源下发展我的研究项目。教育 与这项建议有关的是母胎免疫学、生物信息学和胎儿发育， 这将使我能够补充我之前在分子病毒学方面的训练，并开发出一种创新的 寨卡病毒感染者的免疫反应是什么？ 研究项目。妊娠期间感染寨卡病毒（ZIKV）与先天性不孕症有关。 感染和出生缺陷的发展。母体感染导致传播给胎儿， 病毒在整个胎儿组织中传播，导致出生缺陷。有些婴儿出生时情况严重 缺陷和其他缺陷不受影响或仅受到轻微影响。确定以下关系 母胎免疫应答和这些不同的感染表型对于确定 导致胎儿受到有限伤害的母胎免疫反应。这种免疫反应的特征- sponse将为免疫疗法的发展提供靶点，这是降低死亡率所必需的。 和先天性ZIKV感染的发病率。 职业发展计划。我建议的指导和培训活动将侧重于（1）实现 通过指导，提供母胎免疫学、生物信息学和胎儿/婴儿发育方面的专业知识， 动手实验室工作和课程;（2）发展领导技能，以进行调查， 一个独立的实验室;（3）展示和发布数据;（4）继续和扩大专业知识， 专业合作。我的研究将与我的培训活动密切协调， 在该奖项的第四年成功申请R 01。 研究环境。我在明尼苏达大学儿科系得到了很好的支持， 拥有独立实验室空间的威斯康星州。我将继续受益于优秀的合作伙伴- 在我们的机构和非人类灵长类动物设施的主动生物科学研究基础设施 在威斯康星州国家灵长类动物研究中心。

Abstract Candidate. My career goal is to improve the health of children with congenital viral infections by defin- ing the relationship between the fetomaternal immune response and outcomes of congenital infection. My short-term objective is to refine and add to my skills as an independent investigator and begin my independent research career as a junior faculty member at the University of Wisconsin on an acceler- ated trajectory with the protected time and resources to develop my research program. The education linked to this proposal is in the areas of fetomaternal immunology, bioinformatics and fetal development, which will enable me to complement my prior training in molecular virology and develop an innovative approach to the study of the immune response to congenital Zika virus infection. Research Project. Infection with Zika virus (ZIKV) during pregnancy is associated with congenital in- fection and the development of birth defects. Maternal infection results in transmission to the fetus and the virus disseminates throughout fetal tissues resulting in birth defects. Some infants have severe birth defects and others are either not affected or only mildly affected. Determining the relationship between the fetomaternal immune response and these different infection phenotypes is critical for defining the fetomaternal immune response that results in limited fetal harm. Characterization of this immune re- sponse will provide targets for immunotherapy development, which is necessary to reduce the mortality and morbidity from congenital ZIKV infection. Career Development Plan. My proposed mentoring and training activities will focus on (1) attaining expertise in fetomaternal immunology, bioinformatics and fetal/infant development through mentoring, hands-on laboratory work and coursework; (2) developing leadership skills to pursue investigations in an independent laboratory; (3) presenting and publishing data; and (4) continuing and expanding pro- fessional collaborations. My research will be closely coordinated with my training activities and will build toward a successful R01 application in the fourth year of this award. Research Environment. I am well supported within the Department of Pediatrics at the University of Wisconsin with independent laboratory space. I will continue to benefit from the outstanding collabora- tive biological sciences research infrastructure at our institution and nonhuman primate animal facilities at the Wisconsin National Primate Research Center.