Congenital Zika virus (ZIKV) infection results in a range of neurodevelopmental malformations and adverse fetal and infant outcomes. However, evidence from pregnant women with acute ZIKV infection suggests that the virus is not always transmitted to the fetus and that only a subset of fetuses/infants from infected mothers develop detectable neurologic abnormalities. This sub-study will profile the immune response to ZIKV infection in a longitudinal cohort of pregnant women to identify immune response and gene expression signatures associated with protection from vertical transmission of virus and development of sequelae in the offspring, as well as with viral persistance and clinical manifestations in the mother during pregnancy. Whether a robust innate immune response leads to viral clearance and decreased transmission to the fetus will be specifically addressed. Identification of these critical maternal factors is key for the development of therapeutic and preventative interventions. Women in the immunology substudy will have routine sampling as already outlined in ZIP protocol; however, the blood will be collected in different tubes as specified in Table 2 for the proposed assays. In addition, an additional small volume of blood will be collected on 1-2 additional days from women with symptomatic ZIKV infection. With this prospective collection, we will analyze samples from a sub-cohort of women who develop new ZIKV infections (asymptomatic or symptomatic) as compared to ZIKV-negative controls and employ recent advances in high-resolution systems biology technologies to profile individual immune and gene expression signatures and correlate them with ZIP measures of viral persistence and clinical outcomes. Through serial sampling of women throughout pregnancy, we will identify components of innate and adaptive immune mechanisms relevant to resistance and susceptibility to viral persistence in the mother, maternal-fetal transmission of infection, and fetal/newborn infant outcomes. Our results will be critical to guide therapeutic approaches based on maternal immune profiles. Aims: The overall goal of this study is to identify the immune correlates of (a) protection against viral persistance in the mother; (b) protection from maternal to fetal transmission and (c) protection of the developing fetus from microcephaly and other clinical sequelae. Aim 1. Determine the humoral and cellular immunophenotypes generated during the immune response to symptomatic and asymptomatic ZIKV infection in pregnant women, alongside negative controls. Aim 2. Profile responses including cytokine, transcriptional, metabolomic, proteomic, and ancestry/GWAS signatures during symptomatic and asymptomatic ZIKV infection in pregnant women, alongside negative controls. Aim 3. Correlate immune response/phenotype and host transcriptional and metabolomic signatures at the time of infection and during follow-up to a) viral load, viral persistence, and clinical manifestations in the mother; b) vertical transmission of ZIKV to the fetus; and c) clinical outcomes in the fetus and newborn, as assessed by the ZIP study.
|Effective start/end date||6/1/17 → 5/31/18|
- Icahn School of Medicine at Mount Sinai (0255-8661-4609//5U19AI118610-03)
- National Institute of Allergy and Infectious Diseases (0255-8661-4609//5U19AI118610-03)
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